The handling of morphine in patients with a severe CNS trauma/inflammation

When patients with a severe head injury (from trauma or surgery) are given morphine as part of their normal care, the drug is tolerated for a few days and then causes agitation and stimulation. We are suggesting that this is caused by a metabolite of morphine (morphine glucuronide) produced in the liver. This metabolite is normally prevented from entering the brain by a transporter that carries it back into the circulation. We hypothesize that this transporter is lost during the inflammtion that results from the injury. We propose to investigate morphine handling in patients with a brain injury who have a drain inserted into their spinal cord to drain away cerebral spinal fluid. We then can measure the levels of morphine and its metabolites in the fluids around the brain and in the blood. We will be able to tell if the concentration of the irritant metabolite increases as inflammation in the brain increases. Inflammation state will be determined by measuring cytokines in the same fluids. This work could provide an explanation for this unwanted effect of morphine and may lead to a change in drug choice to treat these seriously ill patients.