摘要:

Most human diseases are substantially affected by genetic factors. It now seems clear that the pathogenesis of most diseases lies in complex interactions among the genotype, the environment, and the nature of the process that leads to cell, tissue, organ, or systemic injury. The information derived from the knowledge of the recent completion of the human genome, when combined with the sophisticated tools of molecular biology, will provide the framework for more rapid identification of the genes responsible for susceptibility to disease. Genetic approaches to complex disorders offer great potential to improve our understanding of their pathophysiology, but they also offer significant challenges. There is evidence that cellular and humoral immune responses are subject to polymorphic genetic control, which could explain the well-known diversity of clinical manifestations and outcomes in critically ill patients with the same disease. Therefore, genetic differences between people may affect the likelihood of the development of diseases. Markers of susceptibility will indicate differences in individuals or populations that affect the body's response. The underlying principle of susceptibility markers is the interindividual differences that confer sensitivity or resistance to environmentally induced diseases. This article reviews some of those susceptibility factors for critical illness and acute lung injury.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Reactive oxygen species are reactive, partially reduced derivatives of molecular oxygen (O2). Important reactive oxygen species in biologic systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely related species include the hypohalous acids, particularly hypochlorous acid; chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and its protonated form, peroxynitrous acid, are the most significant reactive nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic processes can generate reactive oxygen species and reactive nitrogen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species and reactive nitrogen species are important in the pathogenesis of acute respiratory distress syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species–mediated or reactive nitrogen species–mediated stress with the development of acute respiratory distress syndrome. Despite these data, pharmacologic strategies directed at minimizing reactive oxygen species–mediated or reactive nitrogen species–mediated damage have yet to be successfully introduced into clinical practice. The most extensively studied compound in this regard isN-acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The clinical relevance of experimental ventilator-induced lung injury has recently received a resounding illustration by the Acute Respiratory Distress Syndrome Network trial that showed a 22% reduction of mortality in patients with acute respiratory disease syndrome when lung mechanical stress was lessened by tidal volume reduction during mechanical ventilation. This clinical confirmation of the concept of ventilator-induced lung injury has also undisputedly substantiated the experimental observation that excessive tidal volume and/or end-inspiratory lung volume is the main determinant of ventilator-induced lung injury. More recently, attention has focused on the roles and implication in the pathogenesis of ventilator-induced lung injury of inflammatory cells and mediators that may be activated and released either in the alveolar space or in the systemic circulation because of the rupture of the alveolar-capillary barrier and on the cellular response to mechanical stress.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The acute respiratory distress syndrome may complicate both pulmonary and extrapulmonary conditions. There is a growing belief that the predisposition to, and clinical course of, the syndrome may be influenced by the extent to which the lung is directly involved in the precipitating pathologic changes. Several studies have highlighted differences in morphology and respiratory physiology between the two subgroups in the early stages of acute respiratory distress syndrome. Further, preliminary reports have suggested that the effects of therapeutic interventions such as alterations in positive end-expiratory pressure, prone ventilation, and the use of inhaled vasoactive agents may differ between pulmonary and extrapulmonary acute respiratory distress syndrome. There are, however, inconsistencies between various studies addressing these issues, which may relate in part to differences in etiologic case mix. There are also practical difficulties in assigning certain cases to one of these two groups. Finally, there are as yet no outcome data to support any modification of clinical management on the basis of this distinction.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Clinical applications of heart-lung interactions have centered on the impact of ventilation on regional blood flow and the measures of cardiovascular responsiveness to both positive end-expiratory pressure and fluid resuscitation. These new and exciting applications of established physiology provide new therapeutic options for the caregiver with reduced risk for complications in the patient. This review illustrates several of these studies within the context of known cardiopulmonary physiology.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

New evidence requires a reinterpretation of the inflation pressure-volume curve and suggests that neither the lower nor the upper inflection point provides reliable information to determine safe ventilator settings in the acute respiratory distress syndrome. Recruitment probably continues throughout the inflation pressure-volume curve, and studies of the deflation pressure-volume curve, reinflations after partial deflation, or decremental positive end-expiratory pressure trials after a recruitment maneuver are probably needed to determine open-lung positive end-expiratory pressure.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Increased knowledge of the pathophysiologic mechanisms of impaired gas exchange during acute respiratory failure during recent years has stimulated many studies that evaluate different treatments to improve oxygenation and outcome. Changes in body position (mainly prone positioning) can significantly improve gas exchange in patients with acute respiratory distress syndrome and acute lung failure, with few complications related to the maneuver; however, no survival advantage has yet been detected. A correlation between aerated lung tissue and oxygenation also confirms the importance of recruitment maneuvers in improving gas exchange. Recent suggestions that recruitment of alveoli proceeds during most of the inspired vital capacity and not only around the lower inflection point of the pressure-volume curve raises the question how to best perform recruitment maneuvers. New data support the hypothesis that maintenance of even small amount of spontaneous breathing during mechanical ventilation (with airway pressure release ventilation or biphasic positive airway pressure) can improve gas exchange, whereas other unconventional ventilatory modes have not yet proved advantageous. Some mechanisms responsible for the high percentage of nonresponse to inhaled nitric oxide have recently been proposed, and combinations of inhaled nitric oxide with other therapies have been tested. Increased knowledge in this area may, in the future, make inhaled nitric oxide more attractive in the treatment of adult respiratory failure as well as in neonatal intensive care.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Three major determinants of lung injury associated with mechanical ventilation have been clearly identified: high pressure/high volume, the shear forces caused by intratidal collapse and decollapse leading to barotrauma/volotrauma/biotrauma. The lung protective strategy aims to reduce the impact of all three determinants. A groundbreaking study showed that reduced tidal volume is less dangerous than high tidal volume, but the researchers did not apply “full” lung protective strategy and did not take into account the shear forces. “Full” protective lung strategy was tested in only one study and in a limited number of patients. Several physiologic studies strongly suggest the advantages of the lung protective strategy.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

On the basis of currently available data, it can be suggested that maintained spontaneous breathing during mechanical ventilation should not be suppressed even in patients with severe pulmonary dysfunction if no contraindications, such as increased intracranial pressure, are present. Improvements in pulmonary gas exchange, systemic blood flow, and oxygen supply to tissues, which have been observed when spontaneous breathing was allowed during ventilatory support, are reflected in the clinical improvement in the patient's condition, as indicated by significantly fewer days with ventilation, earlier extubation, and shorter stays in the intensive care unit. The positive effects of spontaneous breathing have been documented only for some of the available partial ventilatory support modalities. If ventilatory modalities are limited to those whose positive effects have been documented, then partial ventilatory support can be used as a primary modality even in patients with severe pulmonary dysfunction. Whereas controlled mechanical ventilation followed by weaning with partial ventilatory support modalities has been the earlier standard in ventilation therapy, this approach should be reconsidered in view of the available data.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Worldwide, the increasing rates of microbial resistance represent a serious public health problem. Therefore, measures to prevent ventilator-associated pneumonia gain increasing importance. Because antimicrobial treatment in the ICU is a major source of microbial resistance, prevention should be understood not only as the sum of preventive measures but also as part of any management strategy. In this year of review, several important contributions have been made to a better understanding of the relative role of preventive measures. This is particularly true of noninvasive ventilation, continuous aspiration of subglottic secretions, and closed endotracheal suctioning. Management strategies for ventilator-assisted pneumonia remain highly controversial. Despite two decades of vigorous research, there is still no evidence that invasive bronchoscopic techniques should form part of a routine approach to suspected ventilator-assisted pneumonia. Moreover, an impact in terms of important outcome variables could not be consistently demonstrated. In the authors' view, the controversy regarding the relative validity of diagnostic tools should end, and the focus should shift to strategies that define low-risk patients with suspected ventilator-assisted pneumonia who can safely be treated by short-term monotherapy. Finally, several contributions have refined the established treatment regimen. Several new drugs for the treatment of ventilator-assisted pneumonia caused by Gram-positive multiresistant pathogens have been evaluated with promising results.

ISSN:1070-5295    

出版商:OVID    

年代:2002

数据来源: OVID