As modern health care continues to evolve, we expect and are seeing that more sophisticated medical care will be provided outside the traditional acute care environments. Advances in home medical technology, economic pressures, health-care consumerism, and societal changes are all factors playing a role in this evolution. Medically fragile and technology-dependent individuals who were once limited to care in acute and subacute institutional settings are now frequently cared for at home, most often by their immediate family members. Mechanical ventilation has found its way into the patient's home such that physicians and other providers must be prepared for the challenges associated with managing the conditions of complex, ventilator-dependent individuals outside of the walls, controls, and safety of the institutional setting. With little published science and recognized standards of practice, there are fewer rules to guide clinicians through this process. Experience has shown, however, that successful home management of ventilator-dependent individuals can be traced to a smooth and collaborative discharge from the hospital to home. Reimbursement and coverage issues must also be well understood to avoid the aggravation of denials and challenges for necessary equipment and assistance. Once home, a streamlined, patient-centered process supported by effective communication between all care providers can result in a safe and appropriate long-term home ventilation success story.

Conflicts of interest, ubiquitous in medicine, occur when the interests of clinicians do not align with the interests of their patients. When systemic and institutionalized, such conflicts become particularly problematic, not only creating risks for individual patients but also undermining the integrity of the medical profession. Financial conflicts of interest arise when the reimbursement of clinicians appears to encourage decisions and actions that are unlikely to be in the best interest of individual patients. More insidiously, the influence of the pharmaceutical and medical device industry on clinicians, whether through gift giving, support of continuing medical education, or guideline development, creates conflicts of interest that may go unrecognized. Recognition and acknowledgment are the first steps in ameliorating conflicts of interest, which can then be disclosed and potentially eliminated.

Massive pulmonary embolism (PE) is a life-threatening condition with a high early mortality rate due to acute right ventricular failure and cardiogenic shock. As soon as the diagnosis is suspected, an IV bolus of unfractionated heparin should be administered. In addition to anticoagulation, rapid initiation of systemic thrombolysis is potentially life-saving and therefore is standard therapy. Many patients with massive PE cannot receive thrombolysis because of an increased bleeding risk, such as prior surgery, trauma, or cancer. In these patients, catheter or surgical embolectomy are helpful for rapidly reversing right ventricular failure. Catheter thrombectomy appears to be particularly useful if surgical embolectomy is not available or the patient has contraindications to surgery. Although no controlled clinical trials are available, data from cohort studies indicate that the clinical outcomes after surgical and catheter embolectomy may be comparable.

Adult respiratory diseases are caused by many factors, including genetic-environmental interaction. Genetic abnormalities can impact early fetal lung development, postnatal lung maturation, as well as adult lung injury and repair. Studies suggest that abnormally developed lung structure and function may contribute as a susceptibility factor for several adult lung diseases. This review focuses on the relationship between lung development and pathogenesis of several lung diseases including COPD, cystic fibrosis (CF), and asthma. COPD with emphysema has been considered to be an accelerated involutional disease of aging smokers. However, since only a proportion (approximately 15%) of smokers get COPD with emphysema, clearly genetic susceptibility must play a significant part in determining both the age of onset and the rapidity of decline in lung function. In mice, interference with key genes either by null mutation, hypomorphism, or gain or loss of function results in phenotypes comprising either neonatal lethal respiratory distress if the structural effect is severe, or reduced alveolarization and/or early onset emphysema if the effect is milder. Reported susceptibility candidate genes are therefore discussed in some detail, including elastin, lysyl oxidase, fibrillin, the transforming growth factor-beta-Smad3 pathway, as well as extracellular matrix proteases. In the case of CF, the Cftr gene has been shown to regulate fetal lung epithelial cell differentiation and maturation. Subtle abnormalities of lung structure and function are found in clinically asymptomatic CF infants. Finally, airway remodeling due to chronic inflammation is important in infants who later acquire asthma.

Idiopathic pulmonary fibrosis (IPF) remains the most common of the idiopathic interstitial pneumonias and portends a poor prognosis. Significant strides have been made in the approach to diagnosis and in the ability to predict outcome in the last few years. Advances in high-resolution CT (HRCT) scanning have allowed an accurate diagnosis obviating the need for surgical biopsy in many patients. Furthermore, HRCT scanning may aid in determining prognosis and identifying disease progression. The appropriate use of the HRCT scan requires a multidisciplinary iterative approach incorporating all available data to reach a final diagnosis. However, there remains great heterogeneity in disease progression. Pulmonary hypertension and acute exacerbations of IPF negatively influence prognosis and are increasingly a target of therapy. There has been an increase in the number of well-designed clinical trials of IPF that have focused on more specific targets. While no cure has yet been found, each trial expands our understanding regarding the natural course of the disease and the impact of targeted therapy. In the interim, lung transplantation, which appears to improve survival in a subset of IPF patients, remains the only intervention. The objective of this article is to review advances in the understanding of IPF and the evidence for the findings outlined above.

ICU delirium represents a form of brain dysfunction that in many cohorts has been diagnosed in 60 to 85% of patients receiving mechanical ventilation. This organ dysfunction is grossly underrecognized because a majority of patients have hypoactive or "quiet" delirium characterized by "negative" symptoms (eg, inattention and a flat affect) not alarming the treating team. Hyperactive delirium, formerly called ICU psychosis, stands out because of symptoms such as agitation that may cause harm to self or staff, but is actually rare relative to hypoactive delirium and associated with a better prognosis. Delirium is often incorrectly thought to be transient and of little consequence. After adjusting for numerous covariates, delirium is a strong, independent predictor of prolonged length of stay, reintubation, higher mortality, and cost of care. Expanded work on patient safety and recommendations by professional societies have established the importance of delirium monitoring and recommended it as standard practice in ICUs all over the world. This evidence-based review for physicians, nurses, respiratory therapists, and pharmacists will outline why it is imperative that patients be routinely monitored for delirium. This review will discuss modifiable risk factors for delirium, such as metabolic disturbances or potent sedative and analgesic medications. Attention to mitigating risk factors, along with recommended pharmacologic approaches such as antipsychotic medications, may provide resolution of delirium in some patients, while others will persist with refractory brain dysfunction and long-term cognitive impairment following critical illness.

Low-molecular-weight heparin (LMWH) is a popular alternative to unfractionated heparin (UH) for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), in part based on the perception of a lower risk for heparin-induced thrombocytopenia (HIT). To investigate the evidence supporting this perception, we performed a metaanalysis to compare the incidence of thrombocytopenia between LMWH and UH during PE and/or DVT treatment.

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent episodes of upper airway obstruction that result in recurrent arousals and episodic oxyhemoglobin desaturations during sleep. Significant clinical consequences of the disorder cover a wide spectrum, including daytime hypersomnolence, neurocognitive dysfunction, cardiovascular disease, metabolic dysfunction, and cor pulmonale. The major risk factors for the disorder include obesity, male gender, and age. Current understanding of the pathophysiologic basis of the disorder suggests that a balance of anatomically imposed mechanical loads and compensatory neuromuscular responses are important in maintaining upper airway patency during sleep. OSA develops in the presence of both elevated mechanical loads on the upper airway and defects in compensatory neuromuscular responses. A sleep history and physical examination is important in identification of patients and appropriate referral for polysomnography. Understanding nuances in the spectrum of presenting complaints and polysomnography correlates are important for diagnostic and therapeutic approaches. Knowledge of common patterns of OSA may help to identify patients and guide therapy.

Pulmonary embolism in the critically ill requires considerations beyond anticoagulant therapy. Measurements of chamber size by echocardiography and CT and of circulating biomarkers identify higher-risk patients with moderate accuracy and may aid determination of patient acuity. Preserving right ventricular function requires judicious use of volume administration, vasopressor, and perhaps vasodilator therapies. Obstructing thrombus can be treated with fibrinolytic drugs, percutaneous instrumentation, or surgically, but these treatments may not be equally effective or safe. Anticoagulant therapy in critically ill patients is likely best administered IV. Bleeding complications should be assiduously sought but do not necessitate anticoagulant discontinuation in every case. The antidotes protamine, desmopressin acetate, factor VIII inhibitory bypass activity, and recombinant factor VIIa may each have a place in controlling anticoagulant-related bleeding. The grave prognosis of heparin-induced thrombocytopenia warrants close surveillance, with rapid switching to lepirudin, argatroban, or fondaparinux necessary if it is suspected. Retrievable vena cava filters can be lifesaving, and at least one type may be safely removed after residence of nearly 1 year.

In 2001, the Agency for Healthcare Research and Quality recommended the use of ultrasound for the placement of central venous catheters (CVCs) as one of their 11 practices to improve patient care. These recommendations were based on the results of several randomized clinical trials showing significantly improved overall success as well as reductions in complications. This article will describe the practical aspects of using ultrasound to guide placement of CVCs in the internal jugular vein in a "how I do it" approach, as well as review the practice management and training aspects related to incorporating ultrasound into daily practice.

The reported experience is sparse for patients with prior pneumonectomy who are undergoing surgery for ischemic or valvular heart disease. Such surgery poses special technical challenges. To expand the experience with this challenging clinical intervention, we reviewed the reported patients with prior pneumonectomy who were undergoing cardiac surgery as well as the experience at the Cleveland Clinic.

To review the available clinical data supporting the use of probiotics in preventing and treating serious nosocomial infections.

Respiratory diseases remain one of the main causes of morbidity and mortality in the world. Interest has increased as to the possibility of optimizing the repair of the lung with the manipulation of stem cells. Embryonic and adult stem cells have been suggested as possibilities. Adult stem cells have traditionally been thought of as having limited differentiation ability and to be organ specific. However, a series of exciting reports over the last 5 to 10 years have suggested that adult bone marrow-derived stem cells may have more plasticity and are able to differentiate into bronchial and alveolar epithelium, vascular endothelium, and interstitial cell types, making them prime candidates for repair. This article critically reviews the evidence for this plasticity and the use of predominantly adult stem cells to help with lung regeneration and repair and assesses how this technology may be utilized in clinical medicine.

Recently, the concept that stress hyperglycemia in critically ill patients is an adaptive, beneficial response has been challenged. Two large randomized studies demonstrated that maintenance of normoglycemia with intensive insulin therapy substantially prevents morbidity and reduces mortality in these patients. Since then, questions have been raised about the efficacy in general and in specific subgroups, and about the safety of this therapy with regard to potential harm of brief hypoglycemic episodes and of high-dose insulin administration. These issues are systematically addressed in relation to the available evidence. Intensive insulin therapy during intensive care is effective in reducing the mortality and morbidity of critical illness. The available randomized studies show that an absolute reduction in risk of hospital death of 3 to 4% is to be expected from this therapy in an intention-to-treat analysis. In order to confirm this survival benefit and assign it as statistically significant, future studies should be adequately powered, and hence sample size should be at least 5,000. The absolute reduction in the risk of death increases to approximately 8% when patients are treated with intensive insulin for at least 3 days. Data available thus far indicate that blood glucose control to strict normoglycemia is required to obtain the most clinical benefit. The risk of hypoglycemia increases with this therapy, but it remains unclear whether this is truly harmful in the setting of critical care.

Although acute exacerbations of chronic bronchitis (AECBs) are common, there has been no metaanalysis that focused on the optimum regimen.

Hypertension affects > 65 million people in the United States and is one of the leading causes of death. One to two percent of patients with hypertension have acute elevations of BP that require urgent medical treatment. Depending on the degree of BP elevation and presence of end-organ damage, severe hypertension can be defined as either a hypertensive emergency or a hypertensive urgency. A hypertensive emergency is associated with acute end-organ damage and requires immediate treatment with a titratable short-acting IV antihypertensive agent. Severe hypertension without acute end-organ damage is referred to as a hypertensive urgency and is usually treated with oral antihypertensive agents. This article reviews definitions, current concepts, common misconceptions, and pitfalls in the diagnosis and management of patients with acutely elevated BP as well as special clinical situations in which BP must be controlled.

The latest edition of The International Classification of Sleep Disorders: Diagnostic and Coding Manual subsumes a broad range of disorders under the heading "Sleep Related Hypoventilation/Hypoxemic Syndromes." Some are quite common, such as COPD with worsening gas exchange during sleep; while some are exceedingly rare, such as congenital central hypoventilation syndrome. All share the attribute of abnormal gas exchange that worsens, or may only be present, during sleep. The sleep state, the sleeping posture, and the circadian rhythm driving sleep all may affect respiration by altering control of breathing and/or pulmonary mechanics. These changes are largely inconsequential in the normal individual but interact with respiratory, neurologic, or neuromuscular disease to manifest as the sleep-related hypoventilation/hypoxemic syndromes. In addition to optimal treatment of the underlying disorder (when known and when possible), treatment usually involves nocturnal ventilatory support that is now most commonly provided by noninvasive positive pressure ventilation.

Methacholine challenge testing (MCT), also sometimes described as bronchoprovocation testing, is widely performed for both research and diagnostic purposes. MCT is clinically useful when the patient presents with a history of symptoms suggesting asthma, but spirometry findings are normal. Typically, MCT is performed in a pulmonary function laboratory, a clinic, or a physician's office. MCT requires time, effort, and understanding. Two standard testing regimes are identified along with proper coding and reimbursement methodologies.

A consensus panel convened by the American College of Chest Physicians developed guidelines for the treatment of pulmonary arterial hypertension (PAH) that were published in 2004. Subsequently, several important clinical trials have been published, and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues. This article, taking into consideration studies published prior to September 1, 2006, provides an update to the previously published guidelines. The original guidelines have been summarized, a discussion of new studies has been added, and the treatment algorithm has been revised to take into account recent developments in therapy. This update provides evidence-based treatment recommendations for physicians involved in the care of patients with PAH. Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended.

High-frequency oscillatory ventilation (HFOV) is characterized by the rapid delivery of small tidal volumes (Vts) of gas and the application of high mean airway pressures (mPaws). These characteristics make HFOV conceptually attractive as an ideal lung-protective ventilatory mode for the management of ARDS, as the high mPaws prevent cyclical derecruitment of the lung and the small Vts limit alveolar overdistension. In this review, we will summarize the literature describing the use of HFOV in adult patients with ARDS. In addition, we will discuss recent experimental studies of HFOV that have advanced our understanding of its mechanical properties. We identified 2 randomized controlled trials (RCTs) and 12 case series evaluating HFOV in adults with ARDS. In these studies, HFOV appears to be safe and consistently improves oxygenation when used as a rescue mode of ventilation in patients with severe ARDS. The two RCTs comparing HFOV to conventional ventilation revealed encouraging results but failed to show a mortality benefit of HFOV over conventional ventilation. Further research is needed to identify optimal patient selection, technique, the actual Vt delivered, and the role of combining HFOV with other interventions, such as recruitment maneuvers, prone positioning, and nitric oxide.