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。     

容许性高CO_2血症的临床应用

在ARDS等急性呼衰病人中进行机械通气支持时,为了使PaCO_2≤正常水平,势必要用大潮气量(V_T10～15ml·kg~(-1)),其所引起肺泡过张和“容量性损伤”将致病肺进一步受损。为此,提出“容许性高CO_2血症”的新概念。本文就容许性高CO_2血症的由来、理论依据、对机体的影响及临床应用作一综述。     

肺保护性通气策略在腹部和胸部手术中应用的研究进展

肺保护性通气策略(lung protective ventilation strategy,LPVS)的应用是近年来在急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)治疗中的重要进展。ALI/ARDS患者采用保护性通气策略,能够改善气体交换和氧合,降低肺泡及循环内炎性因子的水平,缩短机械通气时间,降低患者病死率[1,2]。但对于非ALI/ARDS需要全身麻醉进行手术的病人,采用LPVS是否受益尚不明确[3]。胸部和腹部手术时间较长、创伤较大,本文对腹部和胸部手术中LPVS应用的研究进展文献总结如下。     

急性呼吸窘迫综合征机械通气治疗

急性肺损伤（acute lungin jury，ALI）是以低氧血症为特征的急性呼吸衰竭，急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是ALI病情进展的结果。机械通气是纠正ARDS低氧血症的主要手段。ARDS的病理生理特点决定了患者机械通气中必须采用特殊的通气策略。     

无泵体外膜氧合在急性呼吸窘迫综合征患者中的临床应用

急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）是指严重感染、休克、创伤及烧伤等非心源性疾病时,肺毛细血管内皮细胞和上皮细胞损伤,造成弥漫性肺间质及肺泡水肿,导致的急性呼吸功能不全或衰竭。以肺容积减少、顺应性下降、严重的通气／血流比例失调为病理生理学特征,发病率为59／10万。各种治疗如反比通气、高频振荡通气、俯卧位通气或液体通气、吸人NO或支气管扩张剂、后期应用糖皮质激素等,使ARDS治疗得到进展,但其病死率仍为30％～50％,肺源性或非肺源性导致的ARDS患者病死率差异无统计学意义。     

通腑泻肺法对ALI／ARDS大鼠血清炎症因子表达的影响

目的观察通腑泻肺法对ALI／ARDS大鼠血清炎症因子的影响,探讨ALI／ARDS肺肠同治的生物学基础。方法将100只健康Wistar大鼠随机分为5组：空白对照组、模型组、治肺组、治肠组和肺肠同治组,采用尾静脉注射油酸加内毒素方法造成大鼠ALI／ARDS模型,观察大鼠血清TNF—a、IT-1β、IL-6、IL-10含量。结果通腑泻肺法可以有效降低大鼠全身炎性因子TNF—a、IL-1β、IL-6、IL-10表达水平。结论（1）通腑泻肺法能够明显减轻ALI／ARDS大鼠免疫炎症损伤,其保护作用较单纯用泻肺法或通腑法效果更有优势;（2）泻肺法、通腑法和通腑泻肺法对ALI／ARDS大鼠血清炎性因子作用靶点不同。     

重症急性胰腺炎并发ALI/ARDS24例临床分析

目的：探讨重症急性胰腺炎并发急性肺损伤（ALI）／急性呼吸窘迫综合征（APDS）的证断与治疗。方法：回顾性分析本院1997年1月至2000年12月收治的28例重症急性胰腺炎中并发的24例ALI／ARDS患者。结果：重症急性胰腺并发ALI／ARDS的发病率高达85．7％,20例为ALI,4例为ARDS,均治愈。结论：在重症急性胰腺炎的急性反应期,应反复测定血气分析,不应拘泥于动脉氧分压数值,当氧合指数（PaO2/FiO2）≤300mmHg,可早期证断出ALI,经积极处理,可避免向ARDS转化。     

急性肺损伤的干细胞治疗研究进展

背景 保护性肺通气治疗可降低急性肺损伤(acute lung injury,ALI)及急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的病死率,但因损伤的肺组织未得到及时修复,其病死率仍居高不下. 目的 审视干细胞疗法对ALI或ARDS的疗效. 内容 阐述间充质干细胞(mesenchymal stem cell,MSC)、胚胎干细胞(embryonic stem cell,ESC)、诱导多能干细胞、内皮祖细胞及内源性肺干细胞治疗ALI的研究进展. 趋向 MSC由于细胞来源广泛、易于分离和增殖、实验证据丰富而最具临床转化前景.     

无创性压力控制通气对外伤引起急性肺损伤呼吸窘迫综合征的治疗

急性肺损伤（ALI）是指心源性以外的各种肺内外致病因素所导致的急性进行性缺氧性呼吸衰竭。临床上以呼吸窘迫,顽固性低氧血症和非心源性肺水肿为特征,其严重阶段称为急性呼吸窘迫综合征（ARDS）,可进一步发展成多器官功能障碍综合征（MODS）。急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）主要治疗方法是应用机械通气技术,     

严重胸外伤致急性肺损伤患者气管切开时机分析

<正>严重胸外伤易并发急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syn-drome,ARDS),如不及时正确处理则易继发肺部感染、肺不张、多脏器功能障碍(MODS)等,死亡率高。机械通气是治疗ALI/ARDS的有效手段。     

Permissive hypercapnia in ARDS and its effect on tissue oxygenation

Many experimental studies have shown that mechanical ventilation with high tidal volumes (V₁) or with a low end-expiratory volume allowing repeated end-expiratory collapse, can result in acute parenchymal lung injury and probably an inflammatory response. Low volume ventilation with permissive hypercapnia has been used in an attempt to avoid such injury in ARDS.
Such management can affect oxygenation in many complex ways. The right-shift of the haemoglobin-oxygen dissociation curve during acute respiratory acidosis may increase venous oxygen tension (PvO₂) which could allow increased O₂ uptake in ischaemic tissues. Acidosis may reduce intrapulmonary shunt (Q_s/Q_t) by potentiating hypoxic pulmonary vasoconstriction, and there may also be direct and autonomically mediated effects of hypercapnia both on the lung vasculature and on the airways. Cardiac output usually increases as a consequence of hypercapnia and perhaps as a result of reduced intrathoracic pressure, further increasing Pv0₂ and CvO₂, but the increase in cardiac output (CO) may tend to increase Q_s/Q_t as flow increases preferentially in unventilated lung. The reduction of mean airway pressure may directly increase Q_s/Q_t. Hypercapnia may affect the distribution of systemic blood flow both within organs and between organs.
Limited clinical studies suggest that tissue oxygenation is usually unchanged or improved during permissive hypercapnia with increased CO₂ reduced arterio-venous O₂ content difference and reduced blood lactate concentration. However, acute hypercapnia per se can reduce lactate production. Further studies are required of this complex issue.     

Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.     

气腹性肺损伤的机制与防治策略

背景 腹腔镜手术具有创伤小、恢复快等特点.但手术过程中建立CO2气腹会造成腹腔内高压和酸碱平衡失调,引起不同程度的肺组织损伤,导致术后肺功能不全,严重者甚至可以发展为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS). 目的 阐述气腹性肺损伤的机制和防治研究新进展. 内容 气腹性肺损伤的发生机制很复杂,可由通气/血流比例失调、氧化和抗氧化系统失衡、缺血/缺氧、缺血/再灌注损伤、促炎和抗炎反应失衡等因素引起.通过小潮气量联合呼气末正压通气的肺通气模式,允许性高碳酸血症,气腹前预处理和药物的应用可以减轻气腹引起的肺损伤. 趋向 通过对CO2气腹引起肺损伤的发生机制及防治策略进行综述,期望为气腹性肺损伤的预防及治疗提供新的思路.     

Pumpless extracorporeal lung assist (pECLA) in patients with acute respiratory distress syndrome and severe brain injury

BACKGROUND: A retrospective analysis was performed to estimate the practicability of a pumpless extracorporeal lung assist system (pECLA) in trauma patients suffering from severe brain injury and the acute respiratory distress syndrome (ARDS). METHODS: Five patients with acute severe brain injury and ARDS, ventilated in a lung protective mode, were connected to pECLA to avoid the detrimental effects of hypercapnia on intracranial pressure (ICP) and cerebral outcome. With pECLA hypercapnia was eliminated in all patients while the minute volume of artificial ventilation could be reduced. Subsequently, ICP was reduced, systemic hemodynamics and cerebral perfusion pressure remained stable. One patient died due to multi-organ failure as a consequence of multi-trauma. The remaining patients survived showing a good neurologic function. CONCLUSIONS: pECLA is a promising alternative compared with conventional pump-driven systems for patients with ARDS and brain injury, since the pECLA system has minor restrictions, limitations and side effects.     

Permissive and Non-permissive Hypercapnia: Mechanisms of Action and Consequences of High Carbon Dioxide Levels

Acute lung injury is a disease with high mortality, which affects a large numbers of patients whose treatment continues to be debated. It has recently been postulated that hypercapnia can attenuate the inflammatory response during lung injury, which would assign it a specific role within lung protection strategies during mechanical ventilation. In this paper, we review current evidence on the role that high levels of CO₂ in the blood play in lung injury. We conclude that, although there are reports that show benefits, the most recent evidence suggests that hypercapnia can be harmful and can contribute to worsening lung damage.     

Beatmung und Volumentherapie beim akuten Lungenversagen

Basic therapy of acute lung injury (ALI) covers a pressure-limited lung protective mechanical ventilation with low tidal volumes (6–8 ml/kg ideal body weight), adequate positive end-expiratory pressure (PEEP) combined with early recruitment maneuvers and a restrictive fluid management (in hypoproteinemic patients preferably with albumin and diuretics). These measures aim at providing sufficient oxygenation while simultaneously minimizing airway pressure, atelectasis and edema formation. The main hemodynamic effects are a decrease in cardiac output and in systemic arterial pressure potentially reducing organ perfusion. However, successful therapy reduces hypoxic pulmonary vasoconstriction and hypercapnia, thus lowering pulmonary artery pressure, unloading the right ventricle, and stabilising hemodynamics.     

Ventilatory management of the severely brain-injured patient

Mechanical ventilation is necessary for treating patients with severe brain injury because it guarantees the airway (through endotracheal intubation), permits sedation (and even curarization), and prevents hypoxemia and/or hypercapnia. Hyperventilation continues to be a focus of debate in the current literature. Nevertheless, the weight of scientific evidence to date suggests that it should not be applied prophylactically during the first 24 hours and that patients should not be hyperventilated for prolonged periods in the absence of intracranial hypertension. Acute lung injury and respiratory distress are among the most frequent and serious complications related to severe brain injury that benefit from the use of positive end-expiratory pressure (PEEP) and ventilation to protect the lung. Gas insufflation through the trachea is a promising therapeutic option for correcting hypercapnia secondary to ventilation for lung protection in such patients. Finally, multimodal monitoring (intracranial pressure, central venous pressure, oxygen saturation detected in the jugular bulb, cerebral oxygen pressure) is recommended for adjusting PEEP and controlling hyperventilation.     

Advances in the management of acute respiratory distress syndrome: protective ventilation

The approach to mechanical ventilation has been revolutionized by new insights into the pathogenesis of respiratory failure in acute respiratory distress syndrome (ARDS). Concepts such as low-volume ventilation, permissive hypercapnia, inverse ratio ventilation, best and intrinsic positive end-expiratory pressure, airway shear, pressure volume curves, inflection points, and prone positioning have radically transformed thinking about ventilator management. Since 1966, more than 8000 ARDS-related publications have appeared. Studies highlighting the experimental basis for innovations in mechanical ventilation are presented. Selected clinical series that exemplify the use of these new strategies are reviewed, to demonstrate how key experimental and clinical research has altered our understanding about what works, and why. Mismanagement of mechanical ventilation causes lung injury and increases mortality. The strategy of protective ventilation has provided the first substantial reduction of mortality in the history of ARDS.     

Permissive Hypercapnia with and without Expiratory Washout in Patients with Severe Acute Respiratory Distress Syndrome

Background: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia.

Methods: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2 O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia.

Results: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO sub 2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2 O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l [center dot] min sup -1 [center dot] m sup -2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01).