ANALGESIC EFFICACY AND SAFETY OF TRAMADOL ENANTIOMERS IN COMPARISON WITH THE RACEMATE - A RANDOMIZED, DOUBLE-BLIND-STUDY WITH GYNECOLOGICALPATIENTS USING INTRAVENOUS PATIENT-CONTROLLED ANALGESIA

The opioid analgesic tramadol is a racemate and consists of 50% (+)- a nd 50% (-)-enantiomer. This study investigated analgesic efficacy and safety of both enantiomers after intravenous (i.v.) injection in compa rison with the racemate. Ninety-eight patients recovering from major g ynaecological surgery under opioid-free halothane anaesthesia were tre ated in a randomised, double-blind study with (+)-tramadol, (-)-tramad ol or the racemate. Following an individualised i.v. loading dose up t o a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. The primary criterion of efficac y was the decrease of pain intensity on a 5-point verbal rating scale from severe or maximum pain to mild or no pain within the first hour a fter the loading dose. The secondary criterion was patient satisfactio n with pain relief during the 24-h observation period stated in the fi nal interview. Patients who terminated the study prematurely were eval uated as non-responders. Of patients treated with (+)-tramadol, tramad ol racemate, and (-)-tramadol, 12%, 15% and 53% of treated patients, r espectively, terminated the study prematurely because of inefficacy. O f patients treated with (+)-tramadol, racemate or(-)-tramadol 67%, 48% and 38%, respectively, were considered responders regarding the prima ry criterion of efficacy (P = 0.061), and 82%, 76% or 41% with respect to the secondary criterion (P = 0.001). Assessment of laboratory scre ening, adverse events, vital signs and blood gas monitoring showed no serious drug-related events. Nausea and vomiting were the most frequen tly reported non-serious side effects and were most often seen with(+) -tramadol. Taking into account both efficacy and safety aspects, the r acemate seems to be superior to either enantiomer alone.