Search

The process of weaning from mechanical ventilation can be complex, requiring collaborative care planning by members of the healthcare team. Improved outcomes have been demonstrated to result from collaborative decision-making processes (e.g., when ventilator teams were utilized). The purpose of this study was to evaluate the effect of a collaborative weaning plan (CWP) on length of time on mechanical ventilation, length of stay in the intensive care unit (ICU), and cost.A new, collaborative weaning plan in the form of a weaning board and flowsheet was introduced into a medical intensive care unit (MICU) setting. A pre- and post-quasi-experimental design using historical controls was used to test the hypotheses. Attempts to control for the effects of history were made by collecting data related to patient, staffing, and organizational variables that could independently effect outcome.MICU in a west coast teaching hospital.Critically ill patients receiving mechanical ventilation for 3 days or greater.Implementation of a collaborative weaning plan.Outcomes studied included length of stay in the MICU, length of time patients were mechanically ventilated in the MICU, cost per MICU stay, and the incidence of complications (e.g., reventilation, readmission to the ICU, and mortality rate).The CWP decreased length of stay in the MICU by 3.6 days (p =.03) and length of ventilator time by 2.7 days (p =.06). There were no significant differences between groups related to cost or incidence of complications.These results support the usefulness of collaborative structures (such as weaning boards/flowsheets) in decreasing ICU length of stay.

The novel three-carbon synthon 1-(1H-1,2, 3-benzotriazol-1-yl)-3-chloroacetone for the synthesis of benzothiazoles, pyrido[1,2-a]indoles, and styryl-substituted indolizines and imidazo[1,2-a]pyridines is reported. The proposed routes are a general and efficient approach for heterocyclizations followed by benzannelations or attachment of arylethenyl pharmacophores.

Interstitial lung disease (ILD) limits exercise capacity through a variety of complex and intriguing mechanisms, including ventilatory limitation, diffusion impairment, and ventilation-perfusion derangement. Resting pulmonary function testing seldom explains the symptoms nor defines the specific pathophysiology of the individual patient. Cardiopulmonary exercise testing can elucidate the relative contributions of these mechanisms and guide therapy. A fundamental problem in ILD is one of inadequate time for lung inflation during intense exercise, resulting in dynamic hypoinflation relative to the ventilatory demand. Pulmonary rehabilitation is underused in ILD. Functional CT imaging may provide insight into the relationship between structural and physiologic abnormalities of regional pulmonary function. Recent advances in nitric oxide research will perhaps further our understanding of the basic pathophysiology of ILD and provide specific treatment for the associated pulmonary vascular disease.

To the Editors: We read with interest the paper by Suissa et al. 1, in which he and his co-authors state that “the effectiveness of inhaled corticosteroids in treating chronic obstructive pulmonary disease remains doubtful.” They review the reported efficacy of inhaled corticosteroids (ICS), noting a lack of pulmonary function improvement but reduction in exacerbation frequency, and a meta-analysis showing reduced mortality 2. However, they conclude that these findings could be biased by methodological problems. One form of bias that they highlight is failure to follow patients after premature withdrawal from randomised clinical trials. Suissa et al. 1 opine that the TORCH (Towards a Revolution in COPD Health) 3 and OPTIMAL 4 studies have provided important evolution in understanding these issues. While both studies used intent-to-treat analysis, …

Pectus excavatum (PE), or funnel chest, is a congenital chest wall deformity in which the sternum is displaced posteriorly due to abnormal bone and cartilage overgrowth. The condition, with an incidence of 1 in 300 births, often worsens in late adolescence and early adulthood with diminished exercise capacity, chest discomfort, palpitations, easy fatigability, and dyspnea with mild exertion. The etiology of pectus excavatum is unknown; however, several mechanisms have been proposed, including underlying defects of the diaphragm. The aim of this study was to evaluate possible regional abnormalities in diaphragmatic motion in PE using real-time dynamic imaging with magnetic resonance. These data were collected as part of a 3-year study evaluating cardiopulmonary function before and after corrective surgery. Ten patients (pre-corrective surgery, mean age = 22.4) with pectus excavatum deformity and 10 control subjects (mean age = 26) were examined with a two-dimensional GRE sequence, at five frames/sec, using a 1.5-Tesla magnetic resonance system (Avanto, Siemens Medical Solutions, Erlangen, Germany). With the subjects in the supine position, one midcoronal (at the level of trachea bifurcation) slice was obtained during two to five deep respiratory cycles for an average of 50 to 100 measurements. Following data acquisition, image processing was performed on a commercially available image processing workstation (Leonardo, Siemens Medical Solutions) for the largest amplitude respiratory cycle. On sequential images, diaphragmatic displacements were measured for three equally spaced locations (lateral, dome, medial) on each hemidiaphragm to calculate superoinferior diaphragmatic displacement rates. With reference lines on a full expiratory image, the absolute diaphragmatic excursions were calculated as the difference between full inspiratory and full expiratory vertical positions. Pectus excavatum patients had statistically significant (p

Background Habitual smoking of alkaloidal cocaine (crack) has been reported to be associated with a number of cardiopulmonary complications that may not be clinically obvious but could potentially interfere with normal physiologic responses to exercise and thus impair maximum exercise performance. Study objective To evaluate the impact of regular use of cocaine on maximum exercise. Design Observational study in crack users and age- and gender-matched control subjects. Subjects Thirty-five habitual cocaine smokers (21 male and 14 female) and 29 age-matched sedentary control nonsmokers of cocaine (15 male and 14 female), all of whom were in good general health. Methods In these subjects, we compared physiologic responses to symptom-limited, incremental maximal exercise performed on a cycle ergometer using a ramp protocol. Comparisons were made for men and women separately. Results For both men and women, long-term cocaine smokers had a reduced aerobic capacity (maximum oxygen consumption) compared with control nonsmokers but did not show evidence of ventilatory limitation, reduced gas exchange threshold, increased physiologic dead space, or gas exchange abnormality at maximum exercise compared with the healthy control subjects. Although cocaine smokers had reduced maximum heart rates compared with control subjects, the relationship between submaximal heart rate and oxygen uptake was normal, indicating a normal cardiovascular response pattern. However, effort perception was similar between the two groups despite the difference in heart rate at maximum exercise, suggesting the possibility of perceptual dysfunction for effort. Differences in aerobic capacity between the crack users and nonusers could not be explained by differences in physical fitness or altered perception of dyspnea. Conclusion In the subjects we studied, long-term cocaine smoking was associated with reduced maximum exercise performance, probably due to poor motivation or altered effort perception. No other identifiable physiologic abnormality appeared to limit exercise in the habitual crack users.

We determined the effect on exercise tolerance and physiological exercise responses of rigorous rehabilitative exercise training in chronic obstructive pulmonary disease (COPD). Fifteen men and 10 women (mean age, 68 +/- 6 yr; FEV1, 0.93 +/- 0.27 L) participated in a rehabilitation program with an exercise component of three per week 45-min sessions of cycle ergometer training for 6 wk with exercise intensity kept near maximal targets. Before and after rehabilitation, patients performed an incremental test and a constant work rate (CWR) test at 80% of the peak work rate in the preprogram incremental test. Ventilation (V(E)) and gas exchange were measured breath by breath; arterialized venous blood was analyzed for blood gas determinations and lactate. Rehabilitation yielded an average increase in peak work rate in the incremental test of 36% (p < 0.001), and in the duration of the CWR test of 77% (p < 0.001). In the CWR test, the kinetics of O2 uptake, CO2 output, V(E), and heart rate were markedly slower than those of healthy subjects. After training, mean response time decrease averaged 17, 22, 34, and 29%, respectively (p < 0.02), evidence of a physiologic training effect. Further, for identical CWR tasks, V(E) was 10% lower (p < 0.02) after training, attributable to altered breathing pattern: tidal volume increased by 8% and respiratory rate decreased by 19%, yielding lower V(D) /V(T) (0.46 versus 0.53 p < 0.005). Rigorous exercise training for patients with severe COPD yields more efficient exercise breathing pattern and lower V(E); this is associated with improved exercise tolerance.

Quantitative structure-activity relationships among some anticoccidial 2-(substituted-phenyl)-1,2,4-triazine-3,5-(2H,4H)-diones were studied by multiple regression analysis (MRA, the Hansch approach) and by linear discriminant analysis (LDA). With MRA the potencies of these compounds are correlated with their reverse-phase HPLC retention times and their 1H NMR chemical shifts at the 6-position. While the coefficients of the variable terms are significant, the moderate R2 (0.56) of the correlating equation suggests that predictions made from this analysis are not likely to be accurate. LDA supports the idea that these descriptors are related to potency, but the discriminant function does not lead to good classification. However, when coupled with a graphic display of the results, LDA gives a more immediate sense of the synthetic direction to take when seeking highly potent analogues. It is apparent that other important but not yet identified factors also play a role in determining the potencies of these compounds.

Christopher B CooperDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USAAbstract: Patients with chronic obstructive pulmonary disease (COPD) exhibit improved exercise capacity after physical training due to reconditioning and improved ventilatory efficiency. Other possible effects are improved ventilatory muscle function and desensitization to dyspnea. We compared general physical training (GPT), consisting of walking and stair climbing exercises, with inspiratory muscle training (IMT), consisting of targeted breathing through inspiratory resistances, in two groups with severe COPD. Seven subjects; age 60 (8) years, forced expiratory volume in one second (FEV1) 0.84 (0.35) L, arterial oxygen tension (PaO2) 11.1 (0.8) kPa, arterial carbon dioxide tension (PaCO2) 4.9 (0.3) kPa, had GPT and nine subjects; age 60 (9) years, FEV1 0.83 (0.31) L, PaO2 10.4 (0.8) kPa, PaCO2 4.4 (0.5) kPa had IMT. Each group trained daily for 30 minutes for eight weeks and 70% of the sessions were supervised. Six minute walking distance increased in both groups: 32 m (6.9% P < 0.05) with GPT and 23 m (4.8%; P

We have evaluated a turbine flow meter (Ventilometer Mark 2, PK Morgan, Kent, UK) at low flow rates and levels of ventilation which are likely to be encountered during exercise in patients with chronic respiratory disease. Pulsatile flows were generated from a volume-cycled mechanical ventilator, the flow wave-form was modified by damping to simulate a human breathing pattern. Comparative measurements of ventilation were made whilst varying tidal volume (VT) from 0.22 to 1.131 and respiratory rate (fR) from 10 to 35 min-1. At lower levels of ventilation the instrument tended to underread especially with increasing fR. The calibration factor must be adjusted to match the level of ventilation if the measurement errors are to be within 5%.

Patients with obstructive and restrictive ventilatory abnormalities suffer from exercise intolerance and dyspnea. Breathing pattern components (volume, flow, and timing) during incremental exercise may provide further insight in the role played by dynamic hyperinflation in the genesis of dyspnea. This study analyzed the breathing patterns of patients with obstructive and restrictive ventilatory abnormalities during incremental exercise. It also explored breathing pattern components with dyspnea at maximum oxygen uptake (VO2 max). Twenty patients, thirteen obstructive patients (forced expiratory volume 38% +/- 13% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 39 +/- 8%), and seven restrictive patients (forced vital capacity 55 +/- 16% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 84% +/- 11%) performed symptom-limited incremental exercise tests on a cycle ergometer with breath-by-breath determination of ventilation and gas exchange parameters. Breathing patterns were analyzed at baseline, 20, 40, 60, 80, and 100 percent of VO2 max. Dyspnea was measured at end-exercise with a 100 mm visual analogue scale. The timing ratio of inspiratory to expiratory time (T(I)/T(E)) and the flow ratio of inspiratory flow to expiratory flow ratio (V(I)/V(E)) were different (p < 0.008) between obstructive and restrictive patients at all exercise intensity levels. The timing components of expiratory time (T(E)) and inspiratory time to total time (T(I)T(TOT)) were significantly different (p < 0.008) at baseline and maximum exercise. Dyspnea scores were not significantly different. For obstructive patients, correlations were noted between T(I)/T(E), V(I)/V(E), T(I)T(TOT) and dyspnea (p < 0.05). Breathing pattern-timing components, specifically T(I)/T(E), in patients with obstructive and restrictive ventilatory abnormalities during exercise provided further insight into the pathophysiology of the two conditions and the contribution of dynamic hyperinflation to dyspnea.

Chronic pulmonary diseases are common in the community and their pathophysiology is complex. The principal symptoms are dyspnea and limited exercise capacity. Some, but not all, patients have true ventilatory limitation where the maximal exercise ventilation (VEmax) equals the measured maximal ventilatory volume (MVV). Those with obstructive disease have impeded expiration requiring an obligatory expiratory time for adequate lung emptying (i.e., a timing constraint). In these patients, increased breathing frequency during exercise tends to lead to hyperinflation and smaller tidal volumes, circumstances that predictably worsen breathing efficiency (i.e., result in high VD/VT). Those with restrictive disease characteristically have limited inspiratory capacity but-unimpeded or even accelerated expiration (i.e. tidal volume constraint). These patients characteristically exhibit rapid respiratory rates (e.g., >50-min−1) at end exercise.

The synthesis of 2-substituted, 3-substituted, and 2,3-disubstituted indoles based on the photolysis of 1-alkenylbenzotriazoles is described along with the application of this method to the synthesis of the 2,3-dihydropyrrolo[1,2-a]indole nucleus of the mitomycin antitumor antibiotics.

The mitomycin analogue 7-methoxymitosene (2) has been prepared in twelve steps through a novel 1-aryltriazole photolysis which serves to generate regiospecifically a highly functionalized indole.

SummaryThe primary abnormality in chronic obstructive pulmonary disease (COPD) is chronic airway inflammation which results in airflow limitation. Disease progression is usually depicted as an accelerated decline in FEV1 over time. However, COPD patients also manifest progressive static hyperinflation due to the combined effects of reduced lung elastic recoil and increased airway resistance. Superimposed on static hyperinflation are further increases in operational lung volumes (dynamic hyperinflation) brought on during exercise, exacerbations or tachypnea.An important consequence of exertional dyspnea is activity limitation. COPD patients have been shown to spend only a third of the day walking or standing compared with age-matched healthy individuals who spend more than half of their time in these activities. Furthermore, the degree of activity limitation measured by an accelerometer worsens with disease progression. COPD patients have been shown to have an accelerated loss of aerobic capacity (VO2max) and this correlates with mortality just as is seen with hypertension, diabetes and obesity. Thus physical inactivity is an important therapeutic target in COPD.Summarizing; airflow obstruction leads to progressive hyperinflation, activity limitation, physical deconditioning and other comorbidities that characterize the COPD phenotype. Targeting the airflow obstruction with long-acting bronchodilator therapy in conjunction with a supervised exercise prescription is currently the most effective therapeutic intervention in earlier COPD. Other important manifestations of skeletal muscle dysfunction include muscle atrophy and weakness. These specific problems are best addressed with resistance training with consideration of anabolic supplementation.

Oxygen supplementation is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Although some COPD patients use oxygen after exercise to relieve dyspnea, the effect of oxygen during recovery from exercise is not clearly understood. Exercise duration and dyspnea recovery time were studied in 18 patients with stable COPD. Patients exercised at a constant submaximal work rate on a treadmill ergometer until they no longer wished to continue. Oxygen, room air and compressed air were randomly administered in three consecutive post-exercise recovery periods. Dyspnea was scored on a 100 mm visual analog scale at 30 s intervals until return to baseline. An additional 20 minute post-recovery resting period was allowed between each test. No significant differences were found in dyspnea recovery time breathing oxygen (271 s), room air (290 s) or compressed air (311 s). When the groups were sorted by sequence of testing, there was a highly significant increase in recovery time (208 s, 307 s and 358 s for the first, second and third tests; P