Inflammation, Infiltration, Necrosis, Abscess and Nicolau Syndrome after Injection of Nonsteroidal Anti-inflammatory Drugs: What is the Reason?

It has been established that some nonsteroidal anti-inflammatory drugs (NSAIDs) when administered through injectable preparations have a local irritating effect, even though the preparations are considered high-quality. It seems that this local irritant action is not related to any specific pharmacological action but with the physicochemical properties of the preparation that grossly violate the homeostasis of the tissues. It seems that the local complications at injection sites can be caused by the nonspecific properties of the injectable preparations: denaturing (cauterizing), hypertonic and acidic activity. Each such property, or their combination, has a locally irritating effect, which can cause abscess, necrosis, and acute aseptic inflammation of reversible or irreversible nature, that follows immediately after subcutaneous or intramuscular administration, a condition named “Nicolau Syndrome”. Conversely, injectable preparations of NSAIDs having isotonic or hypotonic osmolarity associated with a neutral or weakly alkaline pH (about pH 7.4), produce a minimal short-term reversible local inflammatory effect and do not cause Nicolau Syndrome after administration.