The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs

Diaphragmatic fatigue may contribute to the development of respiratory fail ure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent sup ramaximal. bilateral electrophrenic stimulation at a frequency of 20-Hz sti mulation for 30 min. Immediately after the end of a fatigue-producing perio d, Group 1 received no study drug; Group 2 was infused with small-dose prop ofol (0.1 mg/kg initial dose plus 1.5 mg . kg(-1) . h(-1) maintenance dose) ; Group 3 was infused with large-dose propofol (0.1 mg/kg initial dose plus 6.0 mg . kg(-1) . h(-1) maintenance dose). We assessed diaphragmatic contr actility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased f rom baseline values (P < 0.05), whereas there was no change in Pdi at high- frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of prop ofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). C ompared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued valu es (P < 0.05) during propofol administration in Groups 2 and 3. The decreas e in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that p ropofol decreases the contractility of fatigued canine diaphragm in a dose- related fashion.