Chloroprocaine ED₅₀ and ED₉₅ for Propofol Injection Pain Prevention: Dixon's Sequential Method

This study aimed to estimate the median effective dose (ED₅₀) and the 95% effective dose (ED₉₅) of intravenous chloroprocaine (CP), administered pre-emptively for the prevention of propofol-induced injection pain, using Dixon's up-and-down sequential allocation method, and to characterize the associated dose-response relationship.

First, apply a pressure bandage to the elbow of the patient's arm where the peripheral vein is accessible. Then, administer clonprocaine via intravenous injection into the dorsal hand vein while maintaining local pressure from the bandage to block venous return at the elbow for 30 seconds. The initial clonprocaine dose is set at 30mg with 1mg increments. If no injection pain occurs (negative response), reduce the dose by one step for the next patient until pain develops. If pain occurs (positive response), increase the dose by one step until pain subsides. The trial terminates when seven negative and positive responses are recorded, halting case enrollment. Using Probit probability regression analysis, calculate the median effective dose (ED50) and 95% effective dose (ED95) of clonprocaine for preventing propofol injection pain, along with corresponding 95% confidence intervals (CI).

A total of 35 patients completed the study. Of these, 27 reported no pain upon injection, while 8 experienced pain. Probit analysis yielded an ED₅₀ of 11.554 mg (95% CI: 10.096-12.740 mg) and an ED₉₅ of 13.085 mg (95% CI: 12.240-24.151 mg). No vasoactive pharmacologic support was required, and no adverse events related to local anesthetic toxicity were observed.

Intravenous CP, administered at doses of 11.554 mg and 13.085 mg, achieved 50% and 95% efficacy, respectively, in preventing pain associated with propofol injection. These doses were associated with effective attenuation of nociceptive responses, reduced propofol requirements, absence of significant adverse effects, and preservation of hemodynamic stability, thereby supporting the use of CP in enhancing patient comfort during anesthetic induction.