IntroductionMost 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.MethodsWe 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.ResultsGroups 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).ConclusionsAn IMST program can lead to increased MIP and improved weaning outcome in FTW patients compared to SHAM treatment.Trial RegistrationClinicalTrials.gov: NCT00419458

Abstractleukotriene receptor antagonist provide further evidence of the role of leukotrienes Background -A study was undertaken to in the pathogenesis of exercise-induced determine whether montelukast, a new bronchoconstriction. potent cysteinyl leukotriene receptor (Thorax 1997;52:1030-1035 antagonist, attenuates exercise-induced bronchoconstriction. The relationship beKeywords: leukotriene receptor antagonist, exercisetween the urinary excretion of LTE 4 and induced bronchoconstriction, montelukast. exercise-induced bronchoconstriction was also investigated. Methods -Nineteen non-smoking asth-Cysteinyl leukotrienes, synthesised from matic patients with a forced expiratory arachidonic acid through the 5-lipoxygenase volume in one second (FEV 1 ) of [65% of pathway, have an important role in asthma. 1 the predicted value and a reproducible fall Leukotriene C 4 (LTC 4 ) is the dominant metain FEV 1 after exercise of at least 20% were bolite of arachidonic acid released in lung tissue enrolled. Subjects received placebo and but it is very unstable and quickly converted montelukast 100 mg once daily in the even-to leukotriene D 4 (LTD 4 ). In turn, LTD 4 is ing or 50 mg twice daily, each for two days, converted to a less potent metabolite, leukoin a three-period, randomised, double triene E 4 (LTE 4 ), which is excreted in the ilarly against exercise-induced broncho-available, selective, and potent cysteinyl leukoconstriction between plasma concentra-

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We administered dichloroacetate, which prevents or reverses hyperlactatemia in animals and lowers plasma lactate levels in human beings, to 13 patients with lactic acidosis of various causes. All had hypotension, and their acidemia had resisted treatment with sodium bicarbonate. The metabolic effects of dichloroacetate were evaluated in 11 patients. In seven dichloroacetate significantly reduced the level of arterial blood lactate (P less than 0.005) from the base-line value and raised the levels of arterial blood bicarbonate (P less than 0.02) and arterial pH (P less than 0.005). In six of these seven, the acidemia resolved completely with therapy. In 10 of the 13 patients systolic blood pressure increased by 10 to 40 mm Hg, and 4 patients had a 21 per cent increase in cardiac output (P less than 0.02). Despite improvement in their lactic acidemia, all patients but one died of their underlying disease. No serious drug-related toxicity occurred. We conclude that dichloroacetate is a safe and effective adjunct in the treatment of patients with lactic acidosis, although the ultimate prognosis may depend on the underlying disease.