Catálogo de publicaciones - libros

ANP and BNP are secreted from cardiac myocytes in response to atrial or ventricular wall stretch. The physiologic effects of both cardiac natriuretic peptides include natriuresis, diuresis, and inhibition of the activities of several neuroendocrine systems, including the renin-angiotensin-aldosterone system, endothelins, cytokines, and the sympathetic nervous system. Single and serial plasma measurement of BNP is a promising tool for diagnosis and risk stratification of patients with heart failure and acute coronary syndromes. Levels of BNP could also be used to guide drug therapy in these patients. Finally, the administration of nesiritide, a synthetic recombinant human BNP, appears to offer a novel approach in the management of acute heart failure.

Hyaluronan in HMW forms serves as an organizer of the extracellular matrix of the lung, but LMW forms act as signaling molecules that are involved in the production of inflammatory cytokines. LMW hyaluronan is produced either by breakdown of HMW hyaluronan or by synthesis by HAS3. LMW hyaluronan regulates cytokine production through binding to cell surface receptors, CD44, RHAMM and TLRs. We have shown that in VILI, a form of ALI, LMW hyaluronan is produced through upregulation of HAS3 and plays an important role in production of chemokines and neutrophil infiltration found in VILI. LMW hyaluronan-induced IL-8 production in lung cells is dependent on NF-B and JNK/AP-1 activation. Our clinical studies of LMW hyaluronan in patients at risk of ALI and patients with ALI/ARDS suggest that LMW hyaluronan may play an important role in the pathogenesis of ALI/ARDS and may offer targets for new treatment modalities.

Patients with acute brain injury are a unique group of ICU patients. Their indications for intubation and mechanical ventilation are often different from general ICU patients. Therefore, weaning predictors are unique and need to be refined in order to decrease the rate of reintubation while still avoiding prolonged intubation, as both can increase mortality and morbidity. Although tracheostomy may provide a theoretically attractive option for airway management in these patients, potential downsides do exist. Data are limited and the indications and optimal timing for tracheostomy are not well defined. We call for additional studies to investigate this common and important clinical problem.

Pulmonary edema is a common problem in both brain dead organ donors and lung transplant recipients. Based on prior studies of the physiology of the donor lung, there is strong scientific rationale for rigorously testing a strategy aimed at accelerating alveolar fluid clearance and reducing pulmonary edema in organ donors. Use of -agonists to accelerate alveolar fluid clearance in lung recipients might also be therapeutic but further study is needed. Other therapeutic options that warrant investigation include protective ventilatory strategies, diuretics, anti-inflammatory agents, and medications or preservation techniques that preserve or stimulate alveolar fluid clearance in the organ donor. Along with improving donor lung utilization rates, these measures might result in better lung transplant recipient outcomes.

The PFAD system has proved to be an efficient treatment in endotoxic shock in an animal model. This new method of plasma purification utilizes the capacity of the plasma as a means of transport for toxins and can hence be used to bring them to the filters, clearing the organism. Also based on our preliminary results, it appears that extracorporeal treatment using the PFAD system is one of the most promising therapies in treating the dysfunctions related to circulating mediators, such as cytokines, bilirubin, biliary acids and endotoxemia, all of which are the basis of other more complex pathologies (sepsis, systemic inflammatory response syndrome [SIRS], hepatorenal syndrome, chronic and acute liver failure, brain death donors).

Considering the positive results obtained so far, it would be enlightening to study how subjects with other similar medical conditions respond to this system, thus verifying the effectiveness of the PFAD system in other critical diseases.

CPAP is a simple and effective ventilatory treatment for acute respiratory failure related to specific conditions. CPAP (10 cm HO) should be considered as the first-line ventilator treatment for achieving prompt physiologic improvement and lower rates of endotracheal intubation in severe cardiogenic pulmonary edema. CPAP is effective for managing postoperative hypoxemia, enabling improved outcomes in selected patients, provided it is applied for a sufficient period of time. CPAP is also useful during fiberoptic bronchoscopy in hypoxemic patients to prevent subsequent acute respiratory failure. Although application of non-invasive CPAP cannot be generally recommended in the early stage of hypoxemic acute respiratory failure related to ALI/ARDS or pneumonia, CPAP may be beneficial in high-risk, immunocompromised patients. Surprisingly, no study has yet evaluated the effectiveness of early use of CPAP alone in improving outcome in patients with acute exacerbation of COPD. In contrast, use of PEEP/CPAP is often detrimental and is not advisable in other conditions, such as in patients undergoing mechanical ventilation for acute severe asthma.

In conclusion, non-invasive ventilatory support in the neonatal and pediatric ICU has become an option in the last few years and is being applied increasingly. A few uncontrolled trials and case series indicate that the technique can be useful for pediatric patients with a wide spectrum of respiratory disorders including hypoxemic and hypercapnic conditions. The development of more recent techniques and new interfaces can further improve the success of non-invasive respiratory support in this setting. However, the evaluation of the impact of non-invasive respiratory support on morbidity and mortality by appropriate prospective randomized trials and the development of evidence based guidelines for diagnosis, treatment organization and follow up are warranted in the near future.

In view of this slow lung mechanics phenomenon, it is worth considering whether a slow inflation procedure to obtain a quasistatic inspiratory pressure-volume curve has a duration that is sufficient to give adequate information of the slow ‘moulding’ process of the lung. It may be better to use a stepwise up and down PEEP ladder during on-going ventilation where lung mechanics are evaluated with a combination of functional residual capacity measurements and breath-by-breath measurements of volume-dependent compliance. The PEEP ladder functional residual capacity measurements would give data on the slow compliance phenomenon, and the volume-dependent compliance measurements would provide information on the fast compliance. In combination, these measurements may improve the rationale for setting PEEP and tidal volume to minimize lung damage.

Patients with acute brain injury are a unique group of ICU patients. Their indications for intubation and mechanical ventilation are often different from general ICU patients. Therefore, weaning predictors are unique and need to be refined in order to decrease the rate of reintubation while still avoiding prolonged intubation, as both can increase mortality and morbidity. Although tracheostomy may provide a theoretically attractive option for airway management in these patients, potential downsides do exist. Data are limited and the indications and optimal timing for tracheostomy are not well defined. We call for additional studies to investigate this common and important clinical problem.

EIT is a new, portable imaging technique which is increasingly being considered as a future tool for evaluation of the immediate effects of a change in ventilation or other therapeutic intervention in critically ill patients. The method is suitable for monitoring regional lung function directly at the bedside. Steady advances in the development of EIT technology over the past 20 years makes a routine application in a clinical setting in the next decade possible. Nevertheless, further development of both EIT hardware and software is necessary to increase the quality of data, user-friendliness, and clinical acceptance. Proof of clinical efficiency has to be provided. Results of several studies indicate that EIT might be of benefit in optimizing ventilator therapy and minimizing the incidence of ventilator-associated lung injury but this has to be proven in larger clinical studies.