To the Editor:—

Norman et al.  1presented evidence supporting the concept of possible preemptive analgesic effects based on differences in VAS pain at 2 and 4 h after tourniquet inflation in patients receiving the same dose of ketorolac intravenously before and immediately after tourniquet inflation. Their experimental design was carefully conceived, randomized and placebo controlled to minimize the difference between the prestimulus and poststimulus ketorolac plasma concentration. Although they did not measure ketorolac plasma concentration, they probably achieved their goal.

Katz and Siffert 2demonstrated that the concentration of antibiotics under the tourniquet was lower when injected intravenously immediately after tourniquet inflation than before inflation. These findings have dictated the way antibiotics are administered in orthopedics. Indeed, to maximize the concentration at the effector site, antibiotics are injected, preferably before tourniquet inflation, or if this is not done, after tourniquet deflation but not immediately after tourniquet inflation.

The effector site of nonsteroidal antiinflammatory drugs, including ketorolac as one of the antibiotics, is the surgical site. Therefore, Katz and Siffert's 2finding suggests that tissue concentrations of ketorolac below the tourniquet would be significantly lower when the drug is intravenously administered after tourniquet inflation. In these conditions, the difference in VAS pain reported by Norman et al.  1may have reflected the difference in ketorolac concentrations at the effector site, rather than evidence of the preemptive properties of nonsteroidal antiinflammatory drugs. Indeed, VAS pain was higher in patients who received ketorolac immediately after tourniquet inflation, as compared with those who received ketorolac before tourniquet inflation.

Although, like the authors, we intuitively believe that nonsteroidal antiinflammatory drugs have preemptive analgesic effects, Norman et al.  may want to modulate their conclusions. 1 

Norman PH, Daaley MD, Lindsey RW: Preemptive analgesic effects of ketorolac in ankle fracture surgery. A nesthesiology 2001; 94: 599–603
Katz JF, Siffert RS: Tissue antibiotic levels with tourniquet use in orthopedic surgery. Clin Orthop 1982; 165: 261–4