An unusual case of nonsustained ventricular tachycardia.

A 54-year-old woman with advanced cirrhosis secondary to hepatitis C, end-stage kidney failure on hemodialysis, and nonischemic cardiomyopathy was admitted to the medical intensive care unit for treatment of a superior vena cava (SVC) thrombus involving a recently implanted cardioverter-defibrillator (ICD). During her hospitalization, the patient abruptly developed frequent ventricular ectopy with up to 20 beat runs of hemodynamically significant nonsustained ventricular tachycardia. Because ventricular ectopy was not previously seen in the patient, the sudden onset prompted a thorough evaluation. After other causes were excluded, a recently placed scopolamine patch was removed; the ventricular ectopy completely resolved within 24 hours and did not recur for the remainder of the patient's extended hospitalization. While anticholinergic syndrome is associated with a vagally mediated sinus tachycardia, ventricular arrhythmias have not previously been reported with scopolamine, to the best of the authors' knowledge. The observed cardiac side effects of scopolamine rarely occur at therapeutic doses. Scopolamine is metabolized primarily in the liver and excreted by the kidneys, so renal and hepatic impairment should be considered when initiating and dosing this medication. Because anticholinergic medications including scopolamine are commonly used in various clinical settings, we believe that clinicians should be aware of this significant but completely reversible adverse effect.

Novel therapies in asthma: leukotriene antagonists, biologic agents, and beyond.

Asthma is one of the most common conditions seen in clinical practice and carries both a significant disease burden in terms of patient morbidity and a high economic burden in both direct and indirect costs. Despite this, it remains a comparatively poorly understood disease, with only modest advances in treatment over the past decade. Corticosteroids remain the cornerstone of therapy. Both patient compliance with medications and physician adherence to evidence-based guidelines are often poor, and a high percentage of patients continue to have inadequately controlled disease even with optimal therapy. Following a contextual overview of the current treatment guidelines, this review focuses on novel asthma therapies, beginning with the introduction of the leukotriene receptor antagonist zafirlukast in the 1990s, continuing through advanced endoscopic therapy and into cytokine-directed biologic agents currently in development. Along with clinically relevant biochemistry and pharmacology, the evidence supporting the place of these therapies in current guidelines will be highlighted along with data comparing these agents with more conventional treatment. A brief discussion of other drugs, such as those developed for unrelated conditions and subsequently examined as potential asthma therapies, is included.

Inspiratory muscle strength training improves weaning outcome in failure to wean patients: a randomized trial.

INTRODUCTION: Most patients are readily liberated from mechanical ventilation (MV) support, however, 10% - 15% of patients experience failure to wean (FTW). FTW patients account for approximately 40% of all MV days and have significantly worse clinical outcomes. MV induced inspiratory muscle weakness has been implicated as a contributor to FTW and recent work has documented inspiratory muscle weakness in humans supported with MV. METHODS: We conducted a single center, single-blind, randomized controlled trial to test whether inspiratory muscle strength training (IMST) would improve weaning outcome in FTW patients. Of 129 patients evaluated for participation, 69 were enrolled and studied. 35 subjects were randomly assigned to the IMST condition and 34 to the SHAM treatment. IMST was performed with a threshold inspiratory device, set at the highest pressure tolerated and progressed daily. SHAM training provided a constant, low inspiratory pressure load. Subjects completed 4 sets of 6-10 training breaths, 5 days per week. Subjects also performed progressively longer breathing trials daily per protocol. The weaning criterion was 72 consecutive hours without MV support. Subjects were blinded to group assignment, and were treated until weaned or 28 days. RESULTS: Groups were comparable on demographic and clinical variables at baseline. The IMST and SHAM groups respectively received 41.9 ± 25.5 vs. 47.3 ± 33.0 days of MV support prior to starting intervention, P = 0.36. The IMST and SHAM groups participated in 9.7 ± 4.0 and 11.0 ± 4.8 training sessions, respectively, P = 0.09. The SHAM group's pre to post-training maximal inspiratory pressure (MIP) change was not significant (-43.5 ± 17.8 vs. -45.1 ± 19.5 cm H2O, P = 0.39), while the IMST group's MIP increased (-44.4 ± 18.4 vs. -54.1 ± 17.8 cm H2O, P < 0.0001). There were no adverse events observed during IMST or SHAM treatments. Twenty-five of 35 IMST subjects weaned (71%, 95% confidence interval (CI) = 55% to 84%), while 16 of 34 (47%, 95% CI = 31% to 63%) SHAM subjects weaned, P = .039. The number of patients needed to be treated for effect was 4 (95% CI = 2 to 80). CONCLUSIONS: An IMST program can lead to increased MIP and improved weaning outcome in FTW patients compared to SHAM treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00419458.

Five-year results of a phase II trial of hyperfractionated radiotherapy and concurrent daily cisplatin chemotherapy for stage III non-small-cell lung cancer.

The purpose of this study was to evaluate the 5-year results for a phase II trial of hyperfractionated radiotherapy (RT) and concurrent daily cisplatin chemotherapy. Between August 1994 and December 1999, 63 patients with stage IIIA and stage IIIB non-small-cell lung cancer were treated with RT to a dose of 69.6 Gy at 1.2 Gy twice daily with daily cisplatin at 6 mg/m. Thirty-seven patients elected to receive consolidation carboplatin and paclitaxel chemotherapy. Recurrence and survival outcomes were evaluated by Kaplan-Meier analysis. Acute and late side effects were scored by the Radiation Therapy Oncology Group (RTOG) grading system. Radiographic complete or partial tumor response was achieved in 34 of 63 (54%) of cases. Median absolute survival was 20.1 months. Median time to local recurrence and distant metastases were 10.6 and 8.6 months, respectively. Overall survival rates were 57%, 35%, and 23% at 1, 3, and 5 years, respectively. Survival was significantly greater for patients receiving consolidation chemotherapy (50% versus 20% at 3 years). Only 5 patients (7%) experienced Grade 3 or 4 esophagitis. There were 16 cases of Grade 1 or 2 pneumonitis; steroid therapy resolved symptoms in 9 patients. This regimen of hyperfractionated RT and chemotherapy achieved significant response, and 5-year survival rates with acceptable toxicity.

Response to inhaled albuterol during nocturnal asthma.

BACKGROUND: During conventional daytime studies of beta(2)-agonists, 1 puff of a metered-dose inhaler often produces a near maximum bronchodilator response. Consequently, the US Food and Drug Administration-approved dose of albuterol is only 1 to 2 puffs every 4 to 6 hours. OBJECTIVE: To determine whether a higher dose of albuterol is required to normalize lung function during nocturnal asthma. METHODS: Fifteen subjects (age, 18-37 years) were treated with albuterol metered-dose inhalers in a randomized crossover manner at the onset of nocturnal symptoms while sleeping in the Clinical Research Center and during the day when they were asymptomatic. The dose was doubled at 15-minute intervals to 16 cumulative puffs. RESULTS: The mean +/- SD predose FEV(1) was lower at night than during the day (44% +/- 12% vs 68% +/- 9% predicted; P=.0001). The maximum FEV(1) achieved was also lower at night (84% +/- 15% vs 90% +/- 12%; P=.02). The nocturnal dose-response curve was shifted to the right. The median (25th, 75th percentiles) dose required to achieve 80% of the subject's personal best FEV(1) was substantially higher at night (5 [1, 19] vs 0.4 [<0.25, 2] puffs; P=.02), and the median time to achieve this endpoint was longer (47 [21, 90] vs 10 [0.2, 42] minutes; P=.005). No significant systemic effects were observed. CONCLUSION: At night, the response was slower and required a higher dose because more severe airway obstruction was present on awakening. These results suggest that studies establishing the clinical dose of a beta(2)-agonist or assessing the equivalence of different formulations should be conducted in subjects with more severe reversible airway obstruction than is present during conventional daytime studies.

Use of inspiratory muscle strength training to facilitate ventilator weaning: a series of 10 consecutive patients.

BACKGROUND AND PURPOSE: We instituted a low-repetition, high-intensity inspiratory muscle strength training (IMST) program and progressively longer spontaneous breathing periods (SBPs) in a group of medically complex patients who were dependent on mechanical ventilation (MV) and had failed to wean. CASE DESCRIPTIONS: IMST was provided to 10 consecutive patients (four men, six women; mean [+/- SD] age, 59 +/- 15 years) who had failed to wean from MV by conventional methods for >or= 7 days. Prior to initiating IMST, patients had received MV support for a mean of 34 +/- 31 days. Daily IMST consisted of four sets of six breaths through a threshold inspiratory muscle trainer that had been set at an intensity to yield an exertion rating of 6 to 8 of a maximal value of 10. At the start of IMST, patients were tolerating 2.1 +/- 3.4 consecutive hours of SBPs. The duration of the SBPs was increased daily, as tolerated. Patients were considered to have been weaned from MV when they were able to breathe without MV support for 24 consecutive hours. OUTCOMES: After 44 +/- 43 days of IMST, 9 of 10 patients were weaned from MV. The initial IMST pressure was 7 +/- 3 cm H(2)O, and it was increased to 18 +/- 7 cm H(2)O (p < 0.05). DISCUSSION: These results indicate that an IMST protocol that produces significant increases in threshold training pressure, in combination with progressive SBPs, aids in weaning patients from MV. Although promising, these preliminary observations must be tested in a controlled trial.

Efficacy of calcium channel blockers as maintenance therapy for asthma.

AIMS: Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect. The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma. METHODS: Twenty-one otherwise healthy adults with persistent asthma, mean age 25 years, completed treatment with maximum tolerated doses of placebo (P), nifedipine (N), and diltiazem (D) in a double-blind, randomized, three-treatment, three-period, crossover manner, each for 4 weeks. Frequency and severity of asthmatic symptoms were recorded twice daily, as well as peak expiratory flow and frequency of 'prn' use of inhaled terbutaline. Blood pressure, heart rate, P-R interval of the ECG and spirometry were measured biweekly. At the end of each treatment, airway responsiveness to exercise was measured. RESULTS: The mean (s.e. mean)% of days with wheeze was 69plus minus7% during P, 75plus minus6% during N and 72plus minus6% during D (P=0.7). FEV1 was 79plus minus2% of predicted during P, 81plus minus2% during N and 79plus minus2% during D (P=0.6). The decrease in FEV1 after exercise was 32plus minus4% during P, 32plus minus5% during N and 27plus minus4% during D (P=0.5). Heart rate was elevated during N (P=0.0002) whereas P-R interval was prolonged during D (P=0.0001). CONCLUSIONS: Maintenance therapy with calcium channel blockers, at doses that produce cardiovascular effects, do not suppress the signs and symptoms of persistent asthma. Previous bronchoprovocation studies did not predict these results.