Fever is a common problem in ICU patients. The presence of fever frequently results in the performance of diagnostic tests and procedures that significantly increase medical costs and expose the patient to unnecessary invasive diagnostic procedures and the inappropriate use of antibiotics. ICU patients frequently have multiple infectious and noninfectious causes of fever, necessitating a systematic and comprehensive diagnostic approach. Pneumonia, sinusitis, and blood stream infection are the most common infectious causes of fever. The urinary tract is unimportant in most ICU patients as a primary source of infection. Fever is a basic evolutionary response to infection, is an important host defense mechanism and, in the majority of patients, does not require treatment in itself. This article reviews the common infectious and noninfectious causes of fever in ICU patients and outlines a rational approach to the management of this problem.

Endothelial apoptosis can be found in a number of diseases. This review summarizes the current knowledge about the causes and consequences of endothelial apoptosis, and analyzes its possible role in the pathogenesis and treatment of several diseases. Novel forms of therapy based on the proposed pathophysiologic mechanisms are discussed.

There are large reported differences for the carboxyhemoglobin (COHb) half-life (COHb t(1/2)) in humans breathing 100% atmospheric O(2) following CO inhalation in tightly controlled experiments compared to the COHb t(1/2) observed in clinical CO poisoning (range, 36 to 131 min, respectively). Other reports have suggested that the COHb t(1/2) may be affected by gender differences, age, and lung function. We wished to test the hypothesis that the COHb t(1/2) might also be influenced by CO poisoning vs experimental CO exposure, by a history of loss of consciousness (LOC), concurrent tobacco smoking, and by PaO(2). The purpose of the present study was to measure the COHb t(1/2) in a cohort of CO-poisoned patients and to determine if those listed factors influenced the COHb t(1/2).

Tiotropium is a long-acting anticholinergic drug. Studies with cloned human muscarinic receptors show that tiotropium binds equally well to M(1), M(2), and M(3) receptors. However, it dissociates very slowly from M(1) and M(3) receptors compared with ipratropium, and more rapidly from M(2) receptors. Binding studies with [(3)H]tiotropium in human lung show that it is approximately 10-fold more potent than ipratropium. In vitro, tiotropium has a potent inhibitory effect against cholinergic nerve-induced contraction of airways. It dissociates extremely slowly, compared with the dissociation of atropine and ipratropium. Clinical studies with single doses of inhaled tiotropium confirm that it is a potent and long-lasting bronchodilator. Furthermore, it protects against cholinergic bronchoconstriction for > 24 h. Pharmacokinetic studies show that little of the inhaled drug is absorbed, thus predicting a high margin of safety.

Airflow limitation in COPD is a result partially of bronchospasm, but it is also caused by a reduction in airway caliber, the number of small airways, airway collapse because of loss of connective tissue support, excess mucus in the airways, and edema of the airway wall. Structural changes also occur because of long-term destruction of interstitial connective tissue, including elastin. Therefore, in addition to the traditional aim of reversing bronchospasm with bronchodilators, disease-modifying approaches are being investigated. The enzyme neutrophil elastase is implicated in the induction of bronchial disease causing structural changes in lungs, impairment of mucociliary clearance, and impairment of host defenses. The precise mechanism pathway of neutrophil elastase is uncertain, but the effects of influencing the pathway in order to slow disease progression are being investigated. Oxidants may also have a role in the development of COPD, with increased levels activating airway cells and cytokine production.

The traditional approach of caring for patients with chronic respiratory disease has been to rely on pulmonary function tests to quantify the severity and to assess response to therapy. However, patients with respiratory conditions seek medical attention because of symptoms, particularly dyspnea, and impaired ability to function, which clearly impact on an individual's health-related quality of life (HRQOL). Accordingly, instruments have been developed to provide a standardized method to measure health status and levels of impairment. One of the major reasons for measuring HRQOL is to detect how much HRQOL has changed in response to therapy (an evaluative instrument). A minimum clinically significant change has been established for some HRQOL instruments in order to indicate the relative value of any measured change and to guide the interpretation as to whether the change is "clinically meaningful." Selected studies using disease-specific instruments have demonstrated that beta(2)-agonist, anticholinergic, and theophylline medications can improve HRQOL, as compared with placebo therapy.

Sleep has well-recognized effects on breathing, including changes in central respiratory control, airways resistance, and muscular contractility, which do not have an adverse effect in healthy individuals but may cause problems in patients with COPD. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and are most pronounced in rapid eye movement sleep. However, sleep studies are usually only indicated in patients with COPD when there is a possibility of sleep apnea or when cor pulmonale and/or polycythemia are not explained by the awake PaO(2) level. Management options for patients with sleep-related respiratory failure include general measures such as optimizing therapy of the underlying condition; physiotherapy and prompt treatment of infective exacerbations; supplemental oxygen; pharmacologic treatments such as bronchodilators, particularly ipratropium bromide, theophylline, and almitrine; and noninvasive positive pressure ventilation.

Bronchodilator therapy in COPD is deemed successful if it improves ventilatory mechanics to a degree where effective symptom alleviation and increased exercise capacity are achieved. A greater understanding of the pathophysiologic mechanisms of dyspnea and exercise intolerance in COPD has prompted a reevaluation of the manner in which we currently assess therapeutic efficacy. The traditional reliance on an improved postbronchodilator FEV(1) as indicative of a positive clinical response has recognized limitations. To the extent that pharmacologic volume reduction is a desirable therapeutic goal with favorable implications for dyspnea relief and increased exercise tolerance, the potential value of bronchodilator-induced changes in lung volume measurements is currently being studied. It is unlikely, however, given the multifactorial nature of dyspnea and exercise limitation in COPD, that resting spirometric measurements of maximal flows and volumes alone will be sufficiently sensitive to adequately predict a positive clinical response to bronchodilator therapy. Thus, additional direct measurements of exercise dynamic hyperinflation and exercise endurance together with reliable subjective measurements of dyspnea and quality of life are recommended in the setting of a suitable placebo-controlled design.

Effective outpatient management of COPD requires prescription of and adherence to appropriate therapies. Although practice guidelines for outpatient management of COPD are widely available, evidence suggests that these guidelines are not being implemented widely in clinical practice. Furthermore, several studies have shown that patient compliance with recommended therapy is poor. This paper discusses several reasons why implementation of practice guidelines and adherence with prescribed therapies may be poor. Potential clinical and economic consequences of suboptimal management are reviewed. Although the evidence suggests that improved compliance with guideline-recommended practice will improve symptoms and disease-specific quality of life, further work needs to be done to establish the cost-effectiveness of chronic therapies for COPD relative to other chronic conditions. Without such data, managed care organizations will be reluctant to allocate scarce resources toward expensive guideline implementation programs for individuals with this condition.

Three sets of guidelines for the management of COPD that are widely recognized (from the European Respiratory Society [ERS], American Thoracic Society [ATS], and British Thoracic Society [BTS]) are reviewed and compared. None of the documents uses classic evidence-based documentation, and, in many instances, the recommendations are empiric because of a lack of scientific evidence. Overall, there is strong agreement between the documents. All three guidelines recommend inhaled bronchodilators as first-line therapy. Anticholinergics are noted to be well tolerated, although potential problems with beta(2)-agonists are mentioned. The ERS and BTS suggest that inhaled corticosteroids may be of value in patients documented to be steroid responders, whereas the ATS does not recommend their use at all. All three guidelines support the use of oxygen and pulmonary rehabilitation. There are varying levels of disagreement between the guidelines related to the role of spirometry, stratification of disease severity, and the use of theophylline and systemic corticosteroids. Other differences include the role for nebulizers and metered-dose inhalers, secretion clearance methodologies, and the treatment of acute COPD exacerbations and acute respiratory failure. All three guidelines agree that more research is needed to improve our understanding and management of COPD.

COPD is characterized by airflow limitation. The diagnosis is suggested by history and physical examination and is confirmed by spirometry (ie, a low FEV(1) level that is unresponsive to bronchodilators). Once diagnosed, there is no widely accepted staging or severity scoring system. COPD presently is graded using a single measurement such as FEV(1), which, unlike the case with asthma, has a limited role in disease management. A more comprehensive staging system is required incorporating, for example, age, arterial blood gases, dyspnea, body mass index, and distance walked, in addition to FEV(1). These criteria should allow for more evidence-based recommendations for management of this condition. Asthma is an inflammatory disease also characterized by airflow limitation. But in contrast with COPD, the airflow limitation is highly reversible either spontaneously or with therapy. Repeated lung function measurements using portable peak flowmeters have resulted in improved outcomes. Therefore, frequent flow determination is recommended in the routine management of asthma. Treatment with anti-inflammatory agents and close monitoring of lung function should help decrease the morbidity and mortality associated with asthma.

Although considerable progress has been made in understanding the cellular and molecular mechanisms of asthma, much less attention has been paid to COPD. The inflammatory process in COPD is very different from that in asthma, with different inflammatory cells, mediators, inflammatory effects, and response to therapy. Airway inflammation in asthma, characterized by an eosinophilic inflammation affecting all the airways but not lung parenchyma, is linked to airway hyperresponsiveness. In COPD, there is a predominantly neutrophilic inflammation in the airways. Parenchymal destruction is an important irreversible feature and leads to airflow obstruction through dynamic compression. The eosinophilic inflammation in asthma is markedly suppressed by corticosteroids, but they have no appreciable effect on the inflammation in COPD, consistent with a failure of long-term corticosteroids to alter the progression of COPD.

Patient compliance, inhalation devices, and inhalation techniques influence the effectiveness of inhaled medications.

Streptococcus pneumoniae has been known for > 100 years as the most important bacterial pathogen of the respiratory tract in adults and children. In recent years, the pneumococcus has begun to exhibit increasing resistance to antimicrobial agents. Because of the huge number of infections caused by this organism, the development of resistance has changed the approach to many infectious disease problems, particularly with regard to empiric antibiotic therapy and prophylaxis. In our review of the antibiotic-resistant pneumococcus, we review the microbiologic basis for resistance, risk factors for and clinical relevance of infection by a resistant organism, and infection control measures.

We report five cases of status asthmaticus (four requiring mechanical ventilation) that were triggered by inhaled heroin and review the pertinent literature. These cases share common features of sudden and severe asthma exacerbations temporally related to heroin use, stress the importance of considering illicit drug use in like cases, and call attention to a public health issue.

Lactic acidosis often challenges the intensivist and is associated with a strikingly high mortality. Treatment involves discerning and correcting its underlying cause, ensuring adequate oxygen delivery to tissues, reducing oxygen demand through sedation and mechanical ventilation, and (most controversially) attempting to alkalinize the blood with IV sodium bicarbonate. Here we review the literature to answer the following questions: Is a low pH bad? Can sodium bicarbonate raise the pH in vivo? Does increasing the blood pH with sodium bicarbonate have any salutary effects? Does sodium bicarbonate have negative side effects? We find that the oft-cited rationale for bicarbonate use, that it might ameliorate the hemodynamic depression of metabolic acidemia, has been disproved convincingly. Further, given the lack of evidence supporting its use, we cannot condone bicarbonate administration for patients with lactic acidosis, regardless of the degree of acidemia.

Transesophageal echocardiography (TEE) has provided an accurate new window for the evaluation of diseases of the thoracic aorta. Experience with TEE has led to an increased recognition of atherosclerosis of the thoracic aorta as a source of cerebral and systemic embolism. Certain features of aortic plaque morphology detected by TEE may prove to have prognostic and therapeutic significance. The intraoperative assessment of thoracic aortic atherosclerosis by TEE may guide modifications in surgical techniques and aortic manipulations that reduce the incidence of perioperative neurologic complications. TEE has also become a valuable tool for the diagnostic evaluation of patients with blunt chest trauma. The precise role of TEE in the management of these disorders is currently under investigation.

The control of breathing results from a complex interaction involving the respiratory centers, which feed signals to a central control mechanism that, in turn, provides output to the effector muscles. In this review, we describe the individual elements of this system, and what is known about their function in man. We outline clinically relevant aspects of the integration of human ventilatory control system, and describe altered function in response to special circumstances, disorders, and medications. We emphasize the clinical relevance of this topic by employing case presentations of active patients from our practice.