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In the past few years, the use of therapeutic hypothermia as a tool to mitigate neurological injury has gained a firm foothold in many intensive care units (ICU) throughout Europe and, to a lesser degree, in the United States. Currently, in the adult setting its most widespread use is in patients who remain comatose after cardiac arrest. Several studies using historical controls, followed by two randomized controlled trials, have demonstrated that use of induced hypothermia following cardiac arrest improves neurological outcome in patients with witnessed arrests and an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) [,]. These benefits were observed in spite of the fact that the speed of induction of hypothermia (cooling rates) was relatively slow, especially in the larger of the two studies; target temperatures were achieved only after an average period of 8 hours in the multicentered Hypothermia after Cardiac Arrest (HACA) trial []. In the second study, where cooling was initiated very early (in the ambulance during the patients’ transport to the hospital, by administering refrigerated fluids), cooling rates were much faster, although it still took about 2 1/2 hours to reach target temperature []. Regarding the observed benefits, the HACA trial reported an absolute increase in rates of favorable neurological outcome of 16% (relative increase 41%); an absolute increase of 23% (relative increase 88%) was reported in the second study. A meta-analysis by Holzer et al. [] concluded that the number needed to treat to achieve one additional patient with a good neurological outcome was 6, a number that compares very favorably to many other interventions both inside and outside of the ICU setting.

The extracellular matrix has not been well studied in acute lung injury (ALI). We have found that hyaluronan, an organizer of the extracellular matrix, may play an important role in the pathogenesis of ALI. Using an animal model of ventilator-induced lung injury (VILI), a form of ALI, we have found high production of the low molecular weight (LMW) forms of HA that act as non-protein, non-cytokine inflammatory mediators in the lung. This chapter will review the mechanisms involved in the production of LMW hyaluronan and the mechanisms of LMW hyaluronan-induced inflammation in VILI.

Aspiration of gastric and oropharyngeal contents is an important clinical cause of acute lung injury (ALI) that has been recognized for more than 50 years. Epidemiologic studies of ALI, as well as clinical trials, have identified aspiration-induced lung injury as one of the major causes of ALI and the acute respiratory distress syndrome (ARDS) [], []. The most important etiological factor for aspiration-related lung injury is a depressed level of consciousness []. One group of investigators found that an altered level of consciousness was the major predisposing factor in 68% of cases []. Like other clinical disorders that predispose patients to the development of ALI, aspiration of gastric contents may be associated with other clinical risk factors including primary pneumonia, sepsis, hypotension, and drug overdose [].

Lung transplantation is a therapeutic option for patients with end-stage lung or pulmonary vascular disease with an average of 1700 bilateral and single lung transplants performed each year in the United States. Since the 1980s, survival rates for lung transplantation have improved due to advances in surgical techniques, availability of newer immunosuppressive regimens, and enhanced post-operative management. Despite better outcomes, low donor lung utilization rates and a high incidence of primary graft failure are challenges that limit the availability of donor lungs and lung transplant recipient survival, respectively. The objectives of this review are as follows:

Effective airway management is a central part of emergency medicine, and many consider it as an undisputable core skill for emergency physicians []. The failure to establish and maintain adequate gas exchange can be catastrophic and may have important medicolegal implications. Emergency airway management in the field and in the emergency department is often challenging for the physician in charge. Trauma patients pose specific airway problems: unfavorable conditions (e.g., darkness, inadequate space, limited access to the airway, poor patient positioning, unknown assisting personnel with different levels of training, etc.) contribute to failed endotracheal intubation as much as patient peculiarities, e.g., oropharyngeal or pulmonary hemorrhage, facial trauma, or immobilized cervical spine. All these factors, as well as poor skills of physicians themselves, result in a difficult airway in 7–10% of patients who require emergency endotracheal intubation in the field or in the emergency department []–[].

Positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) are probably the most frequently used ventilatory treatments in critically ill patients. In a recent international survey, PEEP was used in more than 90% of patients with acute respiratory distress syndrome (ARDS) and in more than 50% of patients with an exacerbation of chronic obstructive pulmonary disease (COPD) []. PEEP is a technique in which airway pressure is maintained above atmospheric pressure at end expiration by pressurization of the ventilatory circuit, whereas during CPAP, pressure is applied to spontaneous breathing throughout the entire respiratory cycle. Many pathological conditions benefit from the application of PEEP or CPAP, as shown by the pioneering work of Poulton and Oxon [] and Barach and collegues [] who demonstrated that application of positive pressure to the airway can effectively treat patients with cardiogenic pulmonary edema. Nowadays, CPAP or PEEP are used in various forms of acute respiratory failure to improve respiratory mechanics, gas exchange, and cardiac performance.

Ventilation is one of the most expensive therapies in neonatal and pediatric intensive care units (ICUs) [] and a considerable morbidity is associated with its use. The cost of the treatment of preterm neonates, infants and children with respiratory failure, who require mechanical ventilation, is extremely expensive and increases with the length of stay []. Moreover, the financial burden caused from respiratory morbidity for preterm infants who subsequently develop bronchopulmonary dysplasia (BPD) should also be noted. This expense largely reflects nursing and respiratory therapist time, which may be much less in different health care systems worldwide.

Static lung mechanics are considered state of the art in spite of the fact that they only provide a narrow view and do not represent the mechanical behavior of the lung during on-going tidal ventilation. Static measurements are usually cumbersome to perform and are uncommon in clinical practice. There is now ample proof of the importance of choosing a protective ventilatory strategy, which has been defined as ventilating with pressures between the lower and upper inflection point (LIP, UIP) [, ]. Determination of these two inflection points demands static or at least quasi static measurements. The definition of true static conditions is that a sufficiently long end-inspiratory and end-expiratory pause is used to not only stop gas flow in the airways, but also equilibrate visco-elastic forces of the lung tissue. It has been shown that this equilibration time is short and the tracheal pressure decreased as little as ∼ 2 cmHO during the five seconds after instigation of an end-inspiratory pause []. This pressure fall is small compared to the pressure fall that occurs within milliseconds immediately after closing the inspiratory valve of the ventilator. The initial pressure drop is a result of obtaining no-flow conditions in the patient’s airways and the time is correlated to the endotracheal tube and patient airway resistance (R in cmHO/L/s), the breathing circuit compliance (C in l/cmHO) and the flow immediately before closing the valve: t = time constant = R × C In a typical case, the breathing circuit has a compliance of 0.5 × 10 l/cmHO and a tube resistance of 6 cmHO/l/s which gives a time constant of 3 ms. In this case the flow will decrease by 95% in three time constants, i.e., ∼ 10 ms.

The mortality rate and costs associated with acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury (ALI), remain excessively high []. Although the most obvious clinical abnormalities in ALI/ARDS are referable to the lung, the most common cause of death is not due to hypoxia but to multiple organ dysfunction syndrome (MODS) []. MODS is often irreversible with a mortality rate higher than 60%. We currently lack a specific treatment of the syndrome and modern technology, such as hemodialysis, only allows temporary substitution of organ function, providing a bridge to recovery. Better understanding of the pathophysiology leading to the development of MODS in mechanically ventilated patients should help in the development of approaches to interrupt the cascades leading to MODS.

Electrical impedance tomography (EIT) is a non-invasive, radiation-free medical imaging technique invented more than 20 years ago. In 1984, the first EIT tomogram (a cross-sectional image of the human forearm) was generated []. Merely one year later, in 1985, the first EIT scan of the human chest, clearly showing both lungs, followed []. In the following two decades, there was immense development of this method. About twenty research groups, most of them located in Europe, significantly improved EIT hardware and software, identified the major fields of possible future application, and conducted multiple methodological validation studies, as well as experimental animal and clinical studies. Since the early days, the use of EIT in pulmonary applications has been defined as one of the most promising techniques although other applications (e.g., detection or monitoring of breast cancer, pharyngeal and gastric motility, cortical brain activity, pulmonary and peripheral blood perfusion, cardiac performance, urinary bladder emptying, uterus activity) have also been considered []–[].