• Moufida Hamdi, Claude Lentschener, Christophe Bazin, Yves Ozier, and Laurent Havard.
• Anaesthesia and Critical Care Department, Université Paris-Descartes, Faculté de Médecine, Assistance Publique, Hôpitaux de Paris, Hôpital Cochin, Saint Jacques, France.
• Eur J Anaesthesiol. 2009 Jan 1;26(1):23-7.

Background And ObjectiveAdministering various combinations of acetaminophen, ketoprofen, nefopam and ketamine, though sometimes discussed, is expected to provide superior pain relief and reduce opioid analgesic-related side effects. However, some studies have indicated that multimodal analgesia has limited efficacy. We studied the stability of various binary combinations of these four drugs.Patients And MethodsThe drugs were studied at 25 degrees C. Binary mixtures of acetaminophen, ketoprofen, nefopam and ketamine were produced. Each drug concentration was assessed using a specific high-performance liquid chromatographic technique. Measurements were carried out at T0, +1, +2, +4, +6 and +24 h. A 5% loss of initial concentration was considered to be significant. The changes with time of the concentrations were analysed using linear regression analysis. A P value of less than 0.05 was significant.ResultsThe four drugs tested in the binary mixtures were stable, showing neither loss of concentration nor degradation products (P > or = 0.05).ConclusionPhysicochemical negative interaction is not likely to account for the limited clinical efficacy sometimes reported with binary combinations of these drugs. Coadministration of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine from the same bottle or infusion bag using the same venous line is demonstrated to be feasible.

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