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The best intervention to prevent pain on injection with propofol is unknown. We conducted a systematic literature search (Medline, Embase, Cochrane Library, bibliographies, hand searching, any language, up to September 1999) for full reports of randomized comparisons of analgesic interventions with placebo to prevent that pain. We analyzed data from 6264 patients (mostly adults) of 56 reports. On average, 70% of the patients reported pain on injection. Fifteen drugs, 12 physical measurements, and combinations were tested. With IV lidocaine 40 mg, given with a tourniquet 30 to 120 s before the injection of propofol, the number of patients needed to be treated (NNT) to prevent pain in one who would have had pain had they received placebo was 1.6. The closest to this came meperidine 40 mg with tourniquet (NNT 1.9) and metoclopramide 10 mg with tourniquet (NNT 2.2). With lidocaine mixed with propofol, the best NNT was 2.4; with IV alfentanil or fentanyl, it was 3 to 4. IV lidocaine before the injection of propofol was less analgesic. Temperature had no significant effect. There was a lack of data for all other interventions to allow meaningful conclusions. The diameter of venous catheters and speed of injection had no impact on pain.IV lidocaine (0.5 mg/kg) should be given with a rubber tourniquet on the forearm, 30 to 120 s before the injection of propofol; lidocaine will prevent pain in approximately 60% of the patients treated in this manner.