Cynthia Brown

Minimal clinically important differences in the six-minute walk test and the incremental shuttle walking test.

Simple walking tests are widely used for the assessment of functional status in patients with cardiorespiratory disorders. These tests require far less instrumentation than formal cardiopulmonary exercise tests, but they do require standardization of procedures to achieve reproducible results. The most widely used tests for patients with COPD are the 6-minute walking test (6MWT) and the incremental shuttle walking test (SWT). The 6MWT has been characterized in COPD patients with respect to reproducibility and responsivity to change in health status. The 6MWT results are correlated with pulmonary function, health-related quality of life, maximum exercise capacity, and mortality. The minimal clinically important difference (MCID) for the 6MWT is conservatively estimated to be 54–80 meters using both distributional and discriminative methods. For an individual patient, the 6MWT would need to change by about 86 meters to be statistically confident that there has been a change. The SWT has been less extensively validated than the 6MWT, but has similar reproducibility in COPD (CV = approximately 20%). The SWT results improve with pulmonary rehabilitation and bronchodilation, and are highly correlated with maximum oxygen consumption. There are no studies that address the issue of MCID for the SWT. In addition to the MCID, the design and interpretation of COPD clinical trials should take into account the severity of initial impairment, the asymmetry between positive and negative changes, the proportion of patients who show substantial improvement, and the costs and risks of the treatment.

Hypoxia, Not the Frequency of Sleep Apnea, Induces Acute Hemodynamic Stress in Patients With Chronic Heart Failure

OBJECTIVES This study was conducted to evaluate whether brain (B-type) natriuretic peptide (BNP) changes during sleep are associated with the frequency and severity of apneic/hypopneic episodes, intermittent arousals, and hypoxia. BACKGROUND Sleep apnea is strongly associated with heart failure (HF) and could conceivably worsen HF through increased sympathetic activity, hemodynamic stress, hypoxemia, and oxidative stress. If apneic activity does cause acute stress in HF, it should increase BNP. METHODS Sixty-four HF patients with New York Heart Association functional class II and III HF and ejection fraction <40% underwent a baseline sleep study. Five patients with no sleep apnea and 12 with severe sleep apnea underwent repeat sleep studies, during which blood was collected every 20 min for the measurement of BNP. Patients with severe sleep apnea also underwent a third sleep study with frequent BNP measurements while they were administered oxygen. This provided 643 observations with which to relate apnea to BNP. The association of log BNP with each of 6 markers of apnea severity was evaluated with repeated measures regression models. RESULTS There was no relationship between BNP and the number of apneic/hypopneic episodes or the number of arousals. However, the burden of hypoxemia (the time spent with oxygen saturation <90%) significantly predicted BNP concentrations; each 10% increase in duration of hypoxemia increased BNP by 9.6% (95% confidence interval: 1.5% to 17.7%, p = 0.02). CONCLUSIONS Hypoxemia appears to be an important factor that underlies the impact of sleep abnormalities on hemodynamic stress in patients with HF. Prevention of hypoxia might be especially important for these patients.

Field Tests of Exercise in COPD: The Six-Minute Walk Test and the Shuttle Walk Test

Exercise testing is useful to assess the degree of disability, prognosis for survival, presence of exercise-induced hypoxemia, and response to treatment in individuals with chronic obstructive pulmonary disease. Simple walking tests have been developed and are increasingly used in assessment of chronic obstructive pulmonary disease patients for clinical and research purposes. This article reviews how these tests are performed and to what degree they are reliable, and how these tests are used in assessment of individuals with chronic obstructive pulmonary disease.

Exercise Testing in Severe Emphysema: Association with Quality of Life and Lung Function

Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV1 of 26.9 ± 7.1 % predicted. Predicted values for 6MWT and CPX were calculated from reference equations. Correlation coefficients and multivariable regression models were used to determine the association between lung function, quality of life (QOL) scores, and exercise measures. The two forms of exercise testing were correlated with each other (r = 0.57, p < 0.0001). However, the impairment of performance on CPX was greater than on the 6MWT (27.6 ± 16.8 vs. 67.9 ± 18.9 % predicted). Both exercise tests had similar correlation with measures of QOL, but maximum exercise capacity was better correlated with lung function measures than 6-minute walk distance. After adjustment, 6MWD had a slightly greater association with total SGRQ score than maximal exercise (effect size 0.37 ± 0.04 vs. 0.25 ± 0.03 %predicted/unit). Despite advanced emphysema, patients are able to maintain 6MWD to a greater degree than maximum exercise capacity. Moreover, the 6MWT may be a better test of functional capacity given its greater association with QOL measures whereas CPX is a better test of physiologic impairment.

effects of Sleep Apnea on Nocturnal Free Fatty Acids in Subjects with Heart Failure

STUDY OBJECTIVES Sleep apnea is common in patients with congestive heart failure, and may contribute to the progression of underlying heart disease. Cardiovascular and metabolic complications of sleep apnea have been attributed to intermittent hypoxia. Elevated free fatty acids (FFA) are also associated with the progression of metabolic, vascular, and cardiac dysfunction. The objective of this study was to determine the effect of intermittent hypoxia on FFA levels during sleep in patients with heart failure. DESIGN AND INTERVENTIONS During sleep, frequent blood samples were examined for FFA in patients with stable heart failure (ejection fraction < 40%). In patients with severe sleep apnea (apnea-hypopnea index = 65.5 ± 9.1 events/h; average low SpO₂ = 88.9%), FFA levels were compared to controls with milder sleep apnea (apnea-hypopnea index = 15.4 ± 3.7 events/h; average low SpO₂ = 93.6%). In patients with severe sleep apnea, supplemental oxygen at 2-4 liters/min was administered on a subsequent night to eliminate hypoxemia. MEASUREMENTS AND RESULTS Prior to sleep onset, controls and patients with severe apnea exhibited a similar FFA level. After sleep onset, patients with severe sleep apnea exhibited a marked and rapid increase in FFA relative to control subjects. This increase persisted throughout NREM and REM sleep exceeding serum FFA levels in control subjects by 0.134 mmol/L (P = 0.0038). Supplemental oxygen normalized the FFA profile without affecting sleep architecture or respiratory arousal frequency. CONCLUSION In patients with heart failure, severe sleep apnea causes surges in nocturnal FFA that may contribute to the accelerated progression of underlying heart disease. Supplemental oxygen prevents the FFA elevation.

Clinical outcomes associated with high, intermediate, and low rates of failed extubation in an intensive care unit

PURPOSE Extubation failure is associated with adverse outcomes in mechanically ventilated patients, and it is believed that high rates of failed planned extubation (FPE) should be avoided. However, many believe that very low rates may also correlate with adverse outcomes if resulting from overly conservative weaning practices. We examined the relationship between the percentage of FPE (%FPE) and associated outcomes, with the aim of elucidating a favorable middle range. METHODS A total of 1395 extubations were analyzed in mechanically ventilated subjects. Monthly %FPE values were separated into tertiles. Ventilator-free days (VFDs), intensive care unit-free days (IFDs), and mortality were compared among tertiles. RESULTS Monthly %FPE tertiles were as follows: low, less than 7%; intermediate, 7% to 15%; and high, greater than 15%. There were significant differences in VFDs and IFDs by tertile from low to high (VFDs: low, 11.8; intermediate, 12.1; high, 9.9 [P = .003]; IFDs: low, 10.5; intermediate, 10.7; high, 9.0 [P = .033]). Post hoc comparisons demonstrated significant differences between the middle and high tertiles for both VFDs and IFDs. CONCLUSIONS Although exact rates may vary depending on setting, this suggests that a high %FPE (>15) should be avoided in the intensive care unit and that there may be an intermediate range where ventilator outcomes are optimized.

Lung Volume Reduction Surgery

Lung volume reduction surgery (LVRS) has been widely studied and has been available for the treatment of advanced emphysema for 10 years. This paper reviews some of the historical attempts at surgical treatment of emphysema, the physiology of LVRS, and the modern data on patient selection, risks, and benefits. Data from the National Emphysema Treatment Trial are presented in the context of the large body of case series and smaller randomized trials that have preceded that study. Future technologies of bronchoscopic lung volume reduction are also discussed.

A middle rate of failed extubation is desirable?: Questions unanswered (reply).

We have read the research by Kapnadak et al [1] with great interest. In this article, the authors evaluate the differences in clinical outcomes relative to a high, intermediate, or low percentage of failed planned extubation. They describe that the best percentage of failed planned extubation is located in the intermediate range (7%-15%) because, in this range, more ventilator-free days and intensive care unit–free days are observed. Furthermore, no significant difference was found in secondary outcome mortality. In this way, we have some questions. Prolongedweaning is defined as the process that requiredmore than 7 days from the first attempt at withdrawal of mechanical ventilation until extubation, as described by Penuelas [2] and Sellares [3]. This prolonged weaning is associated with a higher rate of failed extubation compared with simple or difficult weaning [2,3]. Therefore, the authors should specify the type of weaning in each subgroup because this could affect the results. Furthermore, the study did not specify the period of mechanical ventilation according to tertile distribution. It is necessary to know this information because an association between prolongedmechanical ventilation and extubation failure has been described [4,5].

The Cushing response evoked by a fourth ventricular brainstem mass.

We report a case of a patient with a mass lesion of the pontomedullary junction with paroxysmal episodes of autonomic and other homeostatic dysfunction that echo the classic Cushing response to intracranial hypertension.1

Acute thrombosis of a separate major coronary artery during initially successful thrombolytic therapy

Intravenous thrombolytic therapy decreases moratherosclerosis but with risk factors (tobacco use, tality in patients with acute myocardial infarction hypercholesterolemia, and a family history of early (MI) and is the standard of care for patients in centers coronary artery disease) presented with acute onset of without access to percutaneous angioplasty [1,2]. The substernal chest pain while playing tennis. The principle action of thrombolytics is to lyse fibrin, patient appeared pale and markedly distressed but rather than dissolve thrombus. Fibrinolysis results in without evidence of heart failure. The initial ECG exposure of clot-bound thrombin and enhancement of revealed ST-elevation in leads V2–V6, I, II and aVL its activity. In addition, thrombin is one of the most and ST-depression in lead III (Fig. 1A). The patient potent platelet activators [3]. Reperfusion failure and was immediately treated with 325 mg of aspirin, early infarct vessel reocclusion, which occur in up to 5000 U of intravenous heparin (followed by contin50% of treated patients [4], are likely associated with uous infusion), intravenous nitroglycerin, and 15 mg platelet activation. This concept is supported by the of t-PA over 2 min followed by 50 mg over 30 min. International Study of Infarct Survival II [2], where The patient continued to have chest pain, and a the addition of aspirin to streptokinase significantly second ECG obtained after the initiation of t-PA lowered mortality compared to streptokinase alone. showed resolution of the ST-elevation in the anterior Occlusion of a second major coronary vessel and lateral leads; however, there was new ST-elevaduring successful thrombolysis of the initial culprit tion in the infero-posterior leads (Fig. 1B). At this artery has not been previously reported. In this case time, the patient was transferred to the cardiac report, we describe a patient who was treated with catheterization laboratory at our institution. t-PA for a large anterior wall MI. After treatment Cardiac catheterization revealed two acute lesions: with thrombolytics, his electrocardiogram (ECG) (1) an ulcerated plaque with a visible thrombus in the showed new ST-elevation in the inferior leads, and proximal left anterior descending (LAD) artery with cardiac catheterization revealed a fresh thrombus in TIMI-3 flow (Fig. 2A); and (2) TIMI-1 flow in the the right coronary artery, suggesting platelet activated right coronary artery (RCA) with an abrupt cut-off, thrombosis induced by thrombolytic therapy. consistent with a thrombus (Fig. 2B). The RCA was A 49-year-old male with no history of coronary treated with angioplasty and intra-coronary adenosine, resulting in a TIMI-3 flow. A 100% thrombotic occlusion in the distal RCA (most likely secondary to *Corresponding author. Present address: Johns Hopkins Hospital, 600 embolized thrombus) was also treated with angioNorth Wolfe Street, Baltimore, MD 21205, USA. E-mail address: sschulma@jhmi.edu (S. Schulman). plasty to 0%. The LAD lesion was not intervened