AEROSOLIZED ATROPINE SULFATE - INFLUENCE OF INHALATION PATTERN ON EFFECTIVE BLOCKADE OF VAGAL AIRWAY TONE

The influence of aerosolized atropine sulfate on airway tone was evaluated in nine healthy adult subjects using three modes of inhalation and a dosimeter to deliver equal doses of aerosol. For six of the subjects additional studies with radioaerosols and scintillation scans were accomplished to qualify lung distributions of deposited aerosol. The three breathing patterns, identified as Tidal, IC, and VC, had average inspiratory volumes of 0.66 +/- 0.1, 2.10 +/- 0.4, and 4.31 +/- 0.9 (SD) L and were initiated from the rest position of the lung for the first two patterns, and residual volume for the third pattern. Total nebulization time and concentration inhaled were identical for each pattern at an atropine dose of 0.025 mg/kg body weight. Average inspiratory flow rates had means of 0.40 +/- 0.1, 0.64 +/- 0.2, and 0.82 +/- 0.2 (SD) L/s tor the respective inhalations. Functional indices of FEV1, MMF, and Vmax50 and anticholinergic side effects were assessed for a 4-h period after aerosol administration. Functional Improvement and duration of effect were maximal with the IC pattern. Within the first hour, absolute Increases in FEV1 averaged 240 ml above baseline (6.2% increase). Increases for MMF and Vmax50 were on average > 23% above baseline (airflow benefit exceeded baseline by 0.91 +/- 0.4 L/s for MMF and 1.14 +/- 0.4 L/s for Vmax50). Except for xerostomia, which was present after all patterns, systemic side effects (tachycardia, blurred vision, and urinary retention) occurred only with VC pattern. Homogeneity and penetration of aerosol deposition were optimal when inhaled with IC pattern, and most central for Tidal pattern (based on planar analysis of radioaerosol deposition in central and peripheral lung regions normalized for regional equilibrium volume).