Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence

To evaluate the effects of clonidine and ephedrine on propofol-induced pain and on hemodynamic changes during the induction sequence.

This was a prospective, randomized, double-blind study.

The study was conducted at a university hospital.

200 ASA physical status I or II adult patients scheduled for elective surgery.

Patients were randomly allocated to one of 4 groups (50 patients per group): clonidine-ephedrine (CE), clonidine-saline (CS), diazepam-ephedrine (DE), and diazepam-saline (DS). Thirty seconds after the administration of ephedrine or saline, propofol 2 mg/kg was infused at a rate of 18.3 mL/min.

Patients were asked whether they had pain due to propofol injection. A blinded investigator evaluated the pain score: 0 = no pain, 1 = mild pain, 2 = severe pain without behavioral signs such as grimace or arm withdrawal movement, and 3 = severe pain accompanied by behavioral signs. Mean arterial blood pressure (MAP) and heart rate (HR) were measured at 1-minute intervals from just before the administration of ephedrine or saline to 5 minutes after the tracheal intubation.

Median pain score in CE was significantly lower than those in the other groups (P < 0.0001). Pain scores in CS and DE were significantly lower than that in DS (P < 0.05). Ephedrine increased HR in CE and DE (P < 0.05), but clonidine did not augment the effect. Mean arterial blood pressure before tracheal intubation decreased to comparable values in all groups. After the intubation, mean arterial blood pressure and HR in CE and CS were significantly lower than those in DE and DS (P < 0.05).

Combination of clonidine and ephedrine effectively reduced propofol-induced pain, but did not prevent propofol-induced hypotension. Clonidine did not augment low dose of ephedrine-induced increase in HR and produced stable hemodynamic condition during the induction sequence.