One of the major goals of bronchodilator therapy in patients with COPD is to decrease airflow limitation in the airways and, as a consequence, improve dyspnea and exercise tolerance. The focus of this systematic review is to assess the effects of treatment with beta-agonists, anticholinergics, and theophyllines on dyspnea, and steady-state and incremental exercise capacity. Thirty-three, double-blind, randomized, placebo-controlled studies written in English were selected. This review shows that approximately half of the studies showed a significant effect of bronchodilator therapy on exercise capacity. Anticholinergic agents have significant beneficial effects in the majority of studies, especially when measured by steady-state exercise protocols. There is a trend toward a better effect of high-dose compared to low-dose anticholinergics. Short-acting beta(2)-mimetics have favorable effects on exercise capacity in more than two thirds of the studies; surprisingly, the situation is less clear for long-acting beta(2)-agents. The majority of the results of the published reports on theophyllines and their effects on exercise are negative. Direct comparisons of different classes of bronchodilators have not been made in a sufficient number of studies for a rational preference. The addition of a second bronchodilator has no proven advantage for improving exercise test results, but this has not been studied extensively and not in sufficiently large studies. The majority of studies reporting a measure of dyspnea found improvements, even in the absence of improvement in exercise capacity.

To compare the sarcoidosis mortality in referral settings (RS) and population-based settings (PS), and to identify the contribution of stage, ethnicity, and corticosteroid therapy (CST) to their disparate outcomes.

A review of the largest observational studies on post-ICU weaning from prolonged mechanical ventilation yields evidence that more than half of such patients can be successfully liberated from mechanical ventilation. Success is likely to fall within a 3-month window, with late successes and partial ventilator independence still possible thereafter. There is a uniformity of practice in finishing difficult weaning with self-breathing trials of increasing duration.

Tracheotomy is commonly performed in ventilator-dependent patients. Disadvantages to the procedure are perioperative complications, long-term airway injury, and the cost of the procedure. Benefits ascribed to tracheotomy vs prolonged translaryngeal intubation include improved patient comfort, more effective airway suctioning, decreased airway resistance, enhanced patient mobility, increased potential for speech, ability to eat orally, a more secure airway, accelerated ventilator weaning, reduced ventilator-associated pneumonia, and the ability to transfer ventilator-dependent patients from the ICU. None of these benefits, however, have been demonstrated in large-scale, prospective, randomized studies. It is proposed that there should be an anticipatory approach wherein tracheotomy is considered after an initial period of stabilization with the patient receiving mechanical ventilation when it becomes apparent that the patient will require prolonged ventilator assistance. Tracheotomy then is performed when the patient appears likely to gain one or more of the benefits ascribed to the procedure.

Weaning techniques include spontaneous breathing trials (SBTs), pressure-support ventilation (PSV), and synchronized intermittent mandatory ventilation (SIMV). SBTs can be conducted using one of several approaches, including T-piece breathing, low-level continuous positive airway pressure, low-level PSV, or setting the ventilator to flow-triggering with no pressure applied to the airway. The SBT can be used as a method to identify extubation readiness or as a weaning technique in which the duration of the trial is gradually increased over time. With pressure-support weaning, the level of pressure support is gradually reduced over time. With weaning using SIMV, the mandatory rate setting on the ventilator is gradually reduced. Randomized controlled trials have reported the poorest weaning outcomes using SIMV. Although new ventilator modes have been introduced to facilitate weaning, to date there is no evidence to support the use of these modes. Noninvasive positive-pressure ventilation also has been reported to facilitate weaning, but the ability to generalize these findings remains to be determined.

In contrast to primarily deductive quantitative research, qualitative research aims to interpret data to develop theoretical insights that describe and explain phenomena such as interactions, experiences, roles, perspectives, and organizations. In this review, we summarize qualitative studies that used primarily in-depth personal interviews as a data collection method and a grounded theory analytic approach. The liberal use of illustrative excerpts and interpretive descriptions offer clinicians vicarious accounts of patient experiences of weaning from mechanical ventilation. Important experiences of patients during their weaning from mechanical ventilation included frustration, uncertainty, hopelessness, fear, and lack of mastery. The extent to which, in at least some patients, these experiences were determinants of weaning failure, consequences of weaning failure, or both, was difficult to establish. An assumption of this genre of research is that if clinicians understand the lived experiences of patients, they can better appreciate patient needs during the weaning process, and by inference, their role as clinicians during weaning from mechanical ventilation.

Health-care professionals (HCPs) can provide protocol-based care that has a measurable impact on critically ill patients beyond their liberation from mechanical ventilation (MV). Randomized controlled trials have demonstrated that protocols for liberating patients from MV driven by nonphysician HCPs can reduce the duration of MV. The structure and features of protocols should be adapted from published protocols to incorporate patient-specific needs, clinician preferences, and institutional resources. As a general approach, shortly after patients demonstrate that their condition has been stabilized on the ventilator, a spontaneous breathing trial (SBT) is safe to perform and is indicated. Ventilator management strategies for patients who fail a trial of spontaneous breathing include the following: (1) consideration of all remediable factors (such as electrolyte derangements, bronchospasm, malnutrition, patient positioning, and excess secretions) to enhance the prospects of successful liberation from MV; (2) use of a comfortable, safe, and well-monitored mode of MV (such as pressure support ventilation); and (3) repeating a trial of spontaneous breathing on the following day. For patients who pass the SBT, the decision to extubate must be guided by clinical judgment and objective data to minimize the risk of unnecessary reintubations and self-extubations. Protocols should not represent rigid rules but, rather, guides to patient care. Moreover, the protocols may evolve over time as clinical and institutional experience with them increases. Useful protocols aim to safely and efficiently liberate patients from MV, reducing unnecessary or harmful variations in approach.

We identified 10 randomized trials that compared alternative management approaches to patient care during and following cardiovascular surgery. One overall strategy involved a modification of anesthesia, in particular, a reduction in the dosage of fentanyl and benzodiazepine or the substitution of fentanyl for propofol (five randomized controlled trials [RCTs]). Pooled results show a shorter duration of ventilation (7 h) and a shorter duration of hospital stay (approximately 1 day) associated with lower anesthetic doses. The second strategy involved early vs late extubation once patients were admitted to the ICU (five RCTs). Pooled results show a shorter duration of ventilation (13 h) and a shorter duration of ICU stay (half a day) associated with early extubation. An additional 8 nonrandomized trials had findings that were consistent with the 10 RCTs. Reintubation, complications, and mortality rates were too low to draw conclusions about these outcomes. Overall, these studies indicate that anesthetic, sedation, and early-extubation strategies in selected cardiac surgery patients are associated with a shorter duration of mechanical ventilation and shorter lengths of ICU and hospital stays.

We found eight randomized controlled trials (RCTs) of miscellaneous interventions that were designed to facilitate the process of weaning from mechanical ventilation. The two RCTs of high-fat/low-carbohydrate enteral nutrition found favorable physiologic effects on CO2 production and respiratory quotient, rendering this type of nutrition potentially useful in patients with impaired ventilatory reserve; however, no conclusions can be made about the outcomes of the duration of ventilation and weaning success. The two RCTs of postextubation use of noninvasive ventilation are conflicting, showing potential short-term physiologic benefit in one study, but no benefit in terms of reintubation rates or other morbidity. These RCTs are less promising than other applications of noninvasive ventilation such as those in patients with COPD exacerbations. One RCT showed no improvement in success of weaning with exogenous growth hormone administration. In the setting of very frequent baseline blood gas analyses, one RCT of oximetry and capnography was associated with significantly fewer blood gas analyses. Biofeedback to enhance safe and rapid weaning showed a dramatically lower duration of ventilation in one RCT that did not report the weaning methods used. One RCT of preextubation acupuncture showed lower rates of laryngospasm in the acupuncture group. Overall, these studies were underpowered for clinically important outcomes. Multidisciplinary, patient-centered, holistic, and non-pulmonary approaches to weaning may provide additional safe, effective adjunctive methods of hastening liberation from mechanical ventilation.

We identified 16 randomized controlled trials (RCTs) of methods for weaning patients from mechanical ventilation, 8 of which were trials of discontinuation assessment strategies, 5 of which were trials of stepwise reduction in mechanical ventilatory support, and 3 of which were trials comparing alternative ventilation modes for weaning periods lasting < 48 h. We found that different thresholds for deciding when a patient is ready for a trial of spontaneous breathing, different criteria for a successful trial, and different thresholds for extubation may overwhelm the impact of alternative ventilation strategies. Nevertheless, the results of these studies suggest the possibility that multiple daily T-piece weaning or pressure support may be superior to synchronized intermittent mandatory ventilation. Other RCTs suggest that early extubation with the back-up institution of noninvasive positive-pressure ventilation as needed may be a useful strategy in selected patients.

We identified 65 observational studies of weaning predictors that had been reported in 70 publications. After grouping predictors with similar names but different thresholds, the following predictors met our relevance criteria: heterogeneous populations, 51; COPD patients, 21; and cardiovascular ICU patients, 45. Many variables were of no use in predicting the results of weaning. Moreover, few variables had been studied in > 50 patients or had results presented to generate estimates of predictive power. For stepwise reductions in mechanical support, the most promising predictors were a rapid shallow breathing index (RSBI) < 65 breaths/min/L (measured using the ventilator settings that were in effect at the time that the prediction was made) and a pressure time product < 275 cm H2O/L/s. The pooled likelihood ratios (LRs) were 1.1 (95% confidence interval [CI], 0.95 to 1.28) for a respiratory rate [RR] of < 38 breaths/min and 0.32 (95% CI, 0.06 to 1.71) for an RR of > 38 breaths/min, which indicate that an RR of < 38 breaths/min leaves the probability of successful weaning virtually unchanged but that a value of > 38 breaths/min leads to a small reduction in the probability of success in weaning the level of mechanical support. For trials of unassisted breathing, the most promising weaning predictors include the following: RR; RSBI; a product of RSBI and occlusion pressure < 450 cm H2O breaths/min/L; maximal inspiratory pressure (PImax) < 20 cm H2O; and a knowledge-based system for adjusting pressure support. Pooled results for the power of a positive test result for both RR and RSBI were limited (highest LR, 2.23), while the power of a negative test result was substantial (ie, LR, 0.09 to 0.23). Summary data suggest a similar predictive power for RR and RSBI. In the prediction of successful extubation, an RR of < 38 breaths/min (sensitivity, 88%; specificity, 47%), an RSBI < 100 or 105 breaths/min/L (sensitivity, 65 to 96%; specificity, 0 to 73%), PImax, and APACHE (acute physiology and chronic health evaluation) II scores that are obtained at hospital admission appear to be the most promising. After pooling, two variables appeared to have some value. An RR of > 38 breaths/min and an RSBI of > 100 breaths/min/L appear to reduce the probability of successful extubation, and PImax < 0.3, for which the pooled LR is 2.23 (95% CI, 1.15 to 4.34), appears to marginally increase the likelihood of successful extubation. Judging by areas under the receiver operator curve for all variables, none of these variables demonstrate more than modest accuracy in predicting weaning outcome. Why do most of these tests perform so poorly? The likely explanation is that clinicians have already considered the results when they choose patients for trials of weaning.

Nosocomial infections (NIs) now concern 5 to 15% of hospitalized patients and can lead to complications in 25 to 33% of those patients admitted to ICUs. The most common causes are pneumonia related to mechanical ventilation, intra-abdominal infections following trauma or surgery, and bacteremia derived from intravascular devices. This overview is targeted at ICU physicians to convince them that the principles of infection control in the ICU are based on simple concepts and that the application of preventive strategies should not be viewed as an administrative or constraining control of their activity but, rather, as basic measures that are easy to implement at the bedside. A detailed knowledge of the epidemiology, based on adequate surveillance methodologies, is necessary to understand the pathophysiology and the rationale of preventive strategies that have been demonstrated to be effective. The principles of general preventive measures such as the implementation of standard and isolation precautions, and the control of antibiotic use are reviewed. Specific practical measures, targeted at the practical prevention and control of ventilator-associated pneumonia, sinusitis, and bloodstream, urinary tract, and surgical site infections are detailed. Recent data strongly confirm that these strategies may only be effective over prolonged periods if they can be integrated into the behavior of all staff members who are involved in patient care. Accordingly, infection control measures are to be viewed as a priority and have to be integrated fully into the continuous process of improvement of the quality of care.

There is extensive experimental evidence from in vitro and animal experiments that congestive heart failure (CHF) is a state of oxidative stress. Moreover, in animal models, the development of CHF is accompanied by changes in the antioxidant defense mechanisms of the myocardium as well as evidence of oxidative myocardial injury. This has led to the hypothesis that oxidative stress may be a mechanism of disease progression in CHF. Indeed, many patients consume antioxidant supplements making the assumption that no harm will result and, possibly, that this therapy will yield some clinical benefits. The focus of this review is to examine the oxidative stress hypothesis of CHF as it pertains to humans. To date, human studies that have sought evidence for a role of oxidative stress in patients with CHF have fallen short of providing strong support for this hypothesis. Studies that have demonstrated an association between oxidant stress and CHF are small and are hindered by methodologic limitations that diminish the impact of their conclusions. Randomized trials of antioxidant supplementation for CHF are scarce, and to our knowledge no study yet convincingly demonstrates any benefit from consuming antioxidant supplements. Therefore, the available evidence is insufficient to support or negate the oxidative stress hypothesis of CHF and the use of antioxidants cannot be recommended as a specific therapy for this condition.

The current therapy for community-acquired lower respiratory tract infections is often empiric, usually involving administration of a beta-lactam or macrolide. However, the increasing prevalence of antibiotic resistance in frequently isolated respiratory tract pathogens has complicated the antimicrobial selection process. This review will discuss the incidence of various respiratory pathogens, as well as update the clinician on the various antimicrobial alternatives available, with particular emphasis on the role of the newer fluoroquinolones in the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia.

Acute pulmonary edema has been associated with cold-water immersion in swimmers and divers. We report on eight divers using a self-contained underwater breathing apparatus (scuba) who developed acute pulmonary edema manifested by dyspnea, hypoxemia, and characteristic chest radiographic findings. All cases occurred in cold water. All scuba divers were treated with complete resolution, and three have returned to diving without further episodes. Mechanisms that would contribute to a raised capillary transmural pressure or to a reduced blood-gas barrier function or integrity are discussed. Pulmonary edema in scuba divers is multifactorial, and constitutional factors may play a role. Physicians should be aware of this potential, likely underreported, problem in scuba divers.

Congestive heart failure (CHF) is a serious medical condition frequently associated with sleep-related breathing disorders, which remain underdiagnosed and undertreated. Recent studies have provided important insight into the pathophysiology of sleep apnea syndrome in patients with CHF, with potential therapeutic implications. In addition to abolition of sleep apnea, continuous positive airway pressure (CPAP) treatment can improve cardiac function and relieve symptoms of CHF. Postulated mechanisms include beneficial hemodynamic effects on ventricular remodeling, unloading of fatigued respiratory muscles, and neurohormonal modulation. Although medium-term studies using CPAP to treat sleep-related breathing disorders associated with CHF have been encouraging, more definitive data from ongoing large clinical trials are necessary to clarify its therapeutic role.

It is well-recognized that the risk of lung cancer declines after smoking cessation. However, the degree of decline in different histologic types of lung cancer is not well understood. We conducted a meta-analysis of peer-reviewed studies to assess the effect of smoking cessation on rates of major histologic types of lung cancer.

Improved understanding of the pathogenesis of acute lung injury (ALI)/ARDS has led to important advances in the treatment of ALI/ARDS, particularly in the area of ventilator-associated lung injury. Standard supportive care for ALI/ARDS should now include a protective ventilatory strategy with low tidal volume ventilation by the protocol developed by the National Institutes of Health ARDS Network. Further refinements of the protocol for mechanical ventilation will occur as current and future clinical trials are completed. In addition, novel modes of mechanical ventilation are being studied and may augment standard therapy in the future. Although results of anti-inflammatory strategies have been disappointing in clinical trials, further trials are underway to test the efficacy of late corticosteroids and other approaches to modulation of inflammation in ALI/ARDS.