Mechanism of action of atracurium on airways

Histamine-releasing drugs may produce significant effects on airways in high-risk populations. To determine if clinically relevant doses of atracurium produce adverse effects on airways, we measured changes in airway resistance in the lung periphery of anesthetized Basenji-Greyhound dogs before and after intravenous (iv) administration of atracurium. A wedged bronchoscope technique was used to measure collateral system resistance (R(cs)). After a stable baseline was obtained, atracurium (1.2 or 0.5 mg/kg) or histamine (200 μg) were administered as an iv bolus, and percent increase in R(cs) was calculated. On separate days dogs were pretreated with the histamine₁ receptor antagonist, chlorpheniramine (0.2 mg/kg iv), with or without atropine (0.2 mg/kg iv) and ranitidine (0.75 mg/kg iv) and the experiment repeated. Histamine (200 μg) increased R(cs) 97 ± 24% at 30 s (8 sublobar segments), whereas a second dose increased R(cs) 77 ± 15%. Pretreatment with chlorpheniramine (0.2 mg/kg iv) totally prevented increases in R(cs) (9 sublobar segments). Atracurium (1.2 mg/kg) increased R(cs) to 174 ± 35% at 3 min (14 sublobar segments), whereas 0.5 mg/kg had little effect (10 sublobar segments). A second bolus of atracurium (1.2 mg/kg) increased R(cs) to only 54 ± 14% (P < 0.01). Chlorpheniramine pretreatment (0.2 mg/kg iv) reduced the response to the initial dose of atracurium to only 26 ± 14% (10 sublobar segments). Pretreatment with a combination of atropine and chlorpheniramine (4 sublobar segments), or ranitidine and chlorpheniramine (5 sublobar segments), did not attenuate the increase in R(cs) significantly more than chlorpheniramine pretreatment alone. We conclude that atracurium produces airway constriction in Basenji-Greyhound dogs and that release of histamine acting on histamine₁ receptors in the airways is important for this effect.