mesna and Bronchial-Diseases

To determine whether bolus instillation of a mucolytic agent (mesna) could diminish airway resistance, endotracheal tube resistance, or both in patients mechanically ventilated for acute respiratory failure.. Randomized, double-blind, placebo-controlled, crossover trial.. Medical-surgical ICU of a county hospital covering 350,000 inhabitants.. Twenty sedated and paralyzed patients with an endotracheal tube (ET) in place more than 72 h.. Data were recorded in three steps: (1) basal; (2) 10 min after endotracheal instillation of 3 mL of either saline solution or mesna; and (3) 10 min after instillation of the opposite drug. A 2-h washout period was allowed between data collection.. We measured tidal volume (VT), inspiratory flow (VI), auto-PEEP, peak pressure (both at airway opening [Pmax.aw] and trachea [Pmax-.tr]) and plateau pressure (Pplat), and we calculated respiratory system compliance (Crs) and the inspiratory resistances of airways+tube (Rmax.aw), airways (Rmax.tr), and ET (Rtube). We found significant differences after the instillation of mesna compared with baseline in the following: airway plus tube resistance (Rmax.aw) (16.9 +/- 7.1 vs 18.9 +/- 7.7 cm H2O); airways resistance (Rmax.tr) (9.8 +/- 6.2 vs 12.0 +/- 6.4 cm H2O), PaO2 (96 +/- 28.5 vs 80 +/- 24.8 mm Hg), PaO2/PAO2 (0.360 +/- 0.152 vs 0.296 +/- 0.127), and PaCO2 (42 +/- 12.9 vs 43 +/- 14.1 mm Hg). We found no changes in compliance, auto-PEEP, and hemodynamics during the study. Instillation of saline solution had no effect on the physiologic variables studied.. In our patients, bolus tracheal instillation of mesna does not improve airway resistance; in fact, mesna instillation induces episodes of bronchospasm that disappear 2 h later.

Topics: Aged; Aged, 80 and over; Airway Resistance; Bronchial Diseases; Constriction, Pathologic; Cross-Over Studies; Double-Blind Method; Female; Hemodynamics; Humans; Intubation, Intratracheal; Male; Mesna; Middle Aged; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Insufficiency

Inhaled medications are widely used in patients suffering from bronchial diseases. Beside their pharmacological properties, nebulised solutions have physico-chemical characteristics that can alter bronchial reactivity. Non-isotonic solutions can induce a bronchial hyperresponsiveness and/or a severe bronchonconstriction. Nevertheless, multiple drugs are used for nebulisation despite their unknown osmolarity. The aim of this study was to measure the tonicity of drug solutions commonly used for nebulisation in patients suffering from bronchial disease. Drug solutions were prepared either according to manufacturer recommendations or by diluting the stock in 5 ml of NaCl (0.9%) or H2CO3 (0.14%). Although bronchodilatator solutions (i.e. salbutamol, terbulatine, ipratropium bromide) were nearly isotonic, some drugs prepared for nebulisation had either a very high (e.g. mesna, netilmicine) or a very low (e.g. gomenol, sodium cromoglycate) tonicity. These values may be responsible for bronchoconstriction. Some hypertonic solutions, prepared with drugs such as acetylcytein or netilmycin, are not commercialised for nebulisation but are commonly used for aerosol therapy. In addition, solutions initially isotonic could become significantly hypertonic towards the end of nebulisation. Taken together, these results suggest that non-isotonic solutions should be used with caution specially in patients with bronchial hyperresponsiveness, even when aerosol therapy is prescribed for upper airways.

Topics: Acetylcysteine; Administration, Inhalation; Aerosols; Albuterol; Anti-Asthmatic Agents; Bicarbonates; Bronchial Diseases; Bronchial Hyperreactivity; Bronchoconstriction; Bronchodilator Agents; Buffers; Chemical Phenomena; Chemistry, Physical; Cromolyn Sodium; Expectorants; Gentamicins; Humans; Hypertonic Solutions; Ipratropium; Isotonic Solutions; Mesna; Nebulizers and Vaporizers; Netilmicin; Oils, Volatile; Osmolar Concentration; Sodium Chloride; Terbutaline; Terpenes