title: Premedication with meloxicam exacerbates intracranial haemorrhage in an immature swine model of non-impact inertial head injury.
abstract: Meloxicam is a cyclo-oxygenase-2 (COX-2) preferential non-steroidal anti-inflammatory drug with very effective analgesic and anti-inflammatory effects in swine. Previous reports in piglets have demonstrated that meloxicam also inhibits COX-1 and reduces production of thromboxane significantly. We use preinjury analgesia in our immature swine (3-5-day-old piglets) model of brain injury using rapid head rotations without impact. In 23 consecutive subjects we found that premedication with meloxicam (n = 6) produced a significantly higher mortality rate (5/6 or 83%) than buprenorphine (n = 17, 1/17 or 6%, P < 0.02). On gross neuropathological examination of the meloxicam-treated swine, we observed massive subdural and subarachnoid bleeding which were not present in buprenorphine-premedicated animals. To our knowledge there are no previous reports in swine of increased bleeding or platelet inhibition associated with meloxicam administration and further research is needed to define mechanisms of action in piglets. We caution the use of meloxicam in swine when inhibition of platelet aggregation might adversely affect refinement of experimental research protocols, such as in stroke, trauma and cardiac arrest models.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399,  USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Friess
authors.forename: M Y
authors.initials: MY
authors.lastname: Naim
authors.forename: T J
authors.initials: TJ
authors.lastname: Kilbaugh
authors.forename: J
authors.initials: J
authors.lastname: Ralston
authors.forename: S S
authors.initials: SS
authors.lastname: Margulies
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications* / Q000401:mortality / Q000473:pathology; D002047:Buprenorphine / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D004195:Disease Models, Animal; D006408:Hematoma, Subdural / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D007273:Injections, Intramuscular; D000077239:Meloxicam; D011292:Premedication; D013345:Subarachnoid Hemorrhage / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013552:Swine / Q000502:physiology*; D013843:Thiazines / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects*
chemical_list: D016564:Amyloid beta-Protein Precursor; D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D002047:Buprenorphine; D000077239:Meloxicam