Dose-response characteristics of midazolam for reducing diaphragmatic contractility

A sedative dose of midazolam decreases contractility of the diaphragm, but no data are available concerning the relationship between dose and diaphrag matic contractility. We studied the dose-response characteristics of midazo lam for reducing the diaphragmatic contractility in dogs. Animals were divi ded into three groups of eight each: Group 1 received no study drug, Group 2 was infused with a sedative dose of midazolam (0.1 mg/kg initial dose plu s 0.1 mg kg(-1) h(-1) maintenance dose), and Group 3 was infused with an an esthetic dose of midazolam (0.1 mg/kg initial dose plus 0.5 mg kg(-1) h(-1) maintenance dose). We assessed the diaphragmatic contractility by transdia phragmatic pressure (Pdi). With an infusion of midazolam in Groups 2 and 3, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decre ased from the baseline values (P < 0.05), and the integrated electrical act ivity of diaphragm (Edi) at 100-Hz stimulation decreased from the baseline values, whereas Edi at 20-Hz stimulation did not change. Compared with Grou p 1, Pdi and Edi for each stimulus decreased during midazolam infusion in G roups 2 and 3 (P < 0.05). The decrease in Pdi and Edi was more in Group 3 t han in Group 2 (P < 0.05). We conclude that midazolam decreases, in a dose- dependent manner, contractility of the diaphragm in dogs.