重症急性胰腺炎并发ARDS的诊断和处理

重症急性胰腺炎（SAP）所致的全身炎症反应综合征（SIRS）能够引起远隔脏器功能发生障碍，其中急性呼吸窘迫综合征（ARDS）为最常见的严重并发症之一，也是早期引起病人死亡和导致多器官功能障碍综合征（MODS），甚至多器官功能衰竭（MOF）的重要原因，其病死率超过40％。因此如何防治SAP病人并发ARDS，对提高SAP疗效具有重要意义。     

Extracorporeal life support for severe acute respiratory distress syndrome in adults

OBJECTIVE: Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. METHODS: We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio < or =100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung "rest" at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. RESULTS: During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH < or =7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. CONCLUSION: Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.     

Airway pressure release ventilation and prone positioning in severe acute respiratory distress syndrome

BACKGROUND: Implementation of lung protective strategy in the treatment of severe Acute Respiratory Distress Syndrome (ARDS) has been reported to be associated with improved outcome. To fulfil this approach, sedation, neuromuscular blocking agents and full mechanical ventilatory support are often used in critical failure of gas exchange. CASE REPORT: We present a patient who developed multiple organ failure, including severe ARDS, after severe skin injuries and septic shock. Ventilatory strategy consisted of lung protective approach, permissive hypercapnia and prone positioning. Airway pressure release ventilation (APRV) with the patient's superimposed spontaneous breathing was implemented and maintained, also during prone episodes. Improvement of gas exhange occurred after application of combined use of APRV and prone positioning. CONCLUSION: APRV and maintenance of patients' spontaneous ventilation is feasible during prone positioning, and this approach may have beneficial synergistic effects on gas exhange in patients with severe acute lung injury.     

Inflammation and the acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of non-cardiogenic pulmonary oedema associated with bilateral pulmonary infiltrates, stiff lungs and refractory hypoxaemia. ARDS is characterized by an explosive acute inflammatory response in the lung parenchyma, leading to alveolar oedema, decreased lung compliance and, ultimately, hypoxaemia. Although our understanding of the causes and pathophysiology of ARDS has increased, the mortality rate remains in the range of 30-50%. No major advances in pharmacological therapy have been achieved. Mechanical ventilation is the main therapeutic intervention in the management of ARDS. The only approach that has been shown to reduce the inflammatory response and mortality is the use of lung-protective ventilatory strategy with a low tidal volume and high positive-end expiratory pressure. This chapter will review the current state of the literature on the pathogenesis of ARDS and ventilatory and pharmacotherapy approaches to its management.     

Mechanical ventilation and acute respiratory distress syndrome

Acute respiratory distress syndrome continues to be a high-mortality condition. The role of mechanical ventilation remains primarily a supportive modality. Recent research has elucidated the adverse impact of traditional ventilation strategies on development of the disease and, ultimately, mortality. The institution of low tidal volume ventilation has been the only intervention that has resulted in definitive improvement in survival. Animal and human investigations that culminated in the Acute Respiratory Distress Syndrome Network low tidal volume study are reviewed. Current controversies in the application of mechanical ventilation including the use of positive end-expiratory pressure, recruitment maneuvers, and high frequency oscillatory ventilation are also addressed.     

The role of neuromuscular blocking drugs in early severe acute respiratory distress syndrome

Background  

Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemic respiratory failure resulting from diffuse lung injury and secondary to direct and indirect insults. Despite advances, mortality remains as high as 40-60%. Neuromuscular blocking agents (NMBAs) are used to facilitate mechanical ventilation in patients with ARDS and have been shown to improve arterial partial pressure of oxygen. However, the association between NMBAs and mortality is unclear. Furthermore, morbidity concerns exist, particularly regarding a putative role in intensive care unit (ICU)-acquired weakness.     

Management of the acute respiratory distress syndrome

Significant advances have occurred in the knowledge of the pathogenesis of ARDS. It is now recognized that ARDS is a manifestation of a diffuse process that results from a complicated cascade of events following an initial insult or injury. Mechanical ventilation and PEEP are still important components of supportive therapy. To avoid ventilator-associated lung injury there is emphasis on targeting ventilator management based on measurement of pulmonary mechanics. For those with resistant hypoxia and severe pulmonary hypertension adjunctive modalities, such as prone positioning and low-dose iNO, may provide important benefit. Alternative modes of supporting gas exchange, such as with partial liquid ventilation and extracorporeal gas-exchange, may serve as rescue therapies. Advances in cell and molecular biology have contributed to a better understanding of the role of inflammatory cells and mediators that contribute to the acute lung injury and the pathophysiology of the syndrome that manifests as ARDS. Based on this new understanding, the potential targets for intervention to ameliorate the systemic inflammatory response have proliferated. Examples include the cytokine network and its receptors, antioxidants, and endothelins. Apart from the challenge of testing these agents in experimental models, it seems likely that determination of the optimum combination of agents will become an equally important endeavor. A particular challenge is to develop better methods of predicting which of the many at-risk patients will go on to full-blown ARDS and MODS, thereby targeting subgroups of patients most likely to benefit from anti-inflammatory therapies. Similarly, the adverse effects of immunosuppressive therapy may be diminished by improved, perhaps molecular, techniques to detect microbial pathogens and permit differentiation between Systemic inflammatory response syndrome and sepsis.     

Pharmacogenetic treatment of acute respiratory distress syndrome

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) occur due to systemic inflammatory disorders or direct injury to the lung. The occurrence of ALI/ARDS is sporadic and is not reliably predicted by the type or severity of injury. A combination of patient characteristics and mechanism of injury are responsible for the sporadic nature of ALI/ARDS and its observed phenotypic variability. Research on the pathophysiology and genetics of ALI/ARDS continues to advance, revealing critical molecular pathways in disease development and specific genetic factors that alter the expression of disease. Despite these advances, pharmacologic therapies have yet to be developed for the prevention or treatment of disease. We anticipate that continued improvement of our understanding of the genetic and pathophysiologic mechanisms underlying ALI/ARDS combined with future clinical trials will allow pharmacogenetic therapies for ALI/ARDS to be developed.     

Large-animal models of acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by an acute inflammatory response that compromises alveolar-capillary membrane integrity. Clinical symptoms include refractory hypoxemia, noncardiogenic edema, and decreased lung compliance. The purpose of this review is to summarize the different ARDS large-animal models in terms of similarity to the clinical disease and underlying pathophysiology. The repeated lavage, oleic acid, endotoxin, and smoke/burn ARDS models will be discussed in this review. While each model has significant benefits, none is without weaknesses. Thus, the choice of large-animal ARDS model must be carefully considered based upon the study focus and investigative team experience.     

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急性肺损伤(acute lung injury，ALI)、急性呼吸窘迫综合征(acute respiratory distress syndrome，ARDS)是指由非静水压原因所导致的肺部一系列病理生理改变继而引起急性、进行性缺氧性呼吸衰竭。ALI和ARDS不是孤立、相互分割的疾病，它们是严重损伤引起机体全身免疫炎征反应失控过程中的不同阶段。从损伤→全身炎症反应综合征     

Pharmacologic strategies in acute respiratory distress syndrome

Treatment of the acute respiratory distress syndrome includes both supportive measures and correction of the underlying cause. Various pharmacological interventions have been proposed to limit the severity of lung injury and enhance the healing process, including exogenous surfactant, inhaled vasodilators (mainly nitric oxide), corticosteroids, prostaglandin E1, antioxidants (N-acetylcysteine), ketoconazole and other substances. Some of these interventions are administered via the airways, for example inhaled nitric oxide or liquid ventilation with perfluorocarbons. Some have beneficial effects on surrogate end-points such as pulmonary gas exchange. However, in large prospective trials none of these pharmacological approaches have resulted in significantly improved survival in acute respiratory distress syndrome patients.     

Metalloproteinase inhibition prevents acute respiratory distress syndrome

BACKGROUND: The acute respiratory distress syndrome (ARDS) occurs in patients with clearly identifiable risk factors, and its treatment remains merely supportive. We postulated that patients at risk for ARDS can be protected against lung injury by a prophylactic treatment strategy that targets neutrophil-derived proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin-induced ARDS model. METHODS: Yorkshire pigs were anesthetized, intubated, surgically instrumented for hemodynamic monitoring, and randomized into three groups: (1) control (n = 4), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 4), infusion of Escherichia coli lipopolysaccharide at 100 microg/kg; and (3) COL-3 + LPS (n = 5), ingestion of COL-3 (100 mg/kg) 12 h before LPS infusion. All animals were monitored for 6 h following LPS or sham LPS infusion. Serial bronchoalveolar lavage (BAL) samples were analyzed for MMP concentration by gelatin zymography. Lung tissue was fixed for morphometric assessment at necropsy. RESULTS: LPS infusion was marked by significant (P < 0.05) physiological deterioration as compared with the control group, including increased plateau airway pressure (P(plat)) (control = 15.7 +/- 0.4 mm Hg, LPS = 23.0 +/- 1.5 mm Hg) and a decrement in arterial oxygen partial pressure (P(a)O(2)) (LPS = 66 +/- 15 mm Hg, Control = 263 +/- 25 mm Hg) 6 h following LPS or sham LPS infusion, respectively. Pretreatment with COL-3 reduced the above pathophysiological changes 6 h following LPS infusion (P(plat) = 18.5 +/- 1.7 mm Hg, P(a)O(2) = 199 +/- 35 mm Hg; P = NS vs control). MMP-9 and MMP-2 concentration in BAL fluid was significantly increased between 2 and 4 h post-LPS infusion; COL-3 reduced the increase in MMP-9 and MMP-2 concentration at all time periods. Morphometrically LPS caused a significant sequestration of neutrophils and monocytes into pulmonary tissue. Pretreatment with COL-3 ameliorated this response. The wet/dry lung weight ratio was significantly greater (P < 0.05) in the LPS group (10.1 +/- 1.0 ratio) than in either the control (6.4 +/- 0.5 ratio) or LPS+COL-3 (7.4 +/- 0.6 ratio) group. CONCLUSIONS: A single prophylactic treatment with COL-3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS.