Continuous Infusion of Tiapride in the Treatment of Hyperactive Delirium – Case Study
Spanish authors recently published a case study of a young man with pharmacologically unmanageable agitation delirium following multiple injuries from a traffic accident, which resolved within 3 days with continuous infusion of tiapride.
Case Description
A 33-year-old man was admitted to the intensive care unit (ICU) with multiple injuries sustained in a traffic accident. He was initially intubated and sedated with propofol and remifentanil. An electroencephalogram (EEG) showed changes consistent with epileptic status, which resolved with the initiation of levetiracetam and phenytoin treatment. Subsequently, the analgesic sedation was adjusted to midazolam and fentanyl. A follow-up EEG showed no further epileptic activity but indicated signs of diffuse encephalopathy.
On the 10th day, as sedation began to be gradually discontinued, hyperactive delirium emerged, which was very difficult to manage pharmacologically. MRI ruled out diffuse axonal injury and showed cortical compression due to subdural hygroma and remnant bleeding in the medial part of the right temporal lobe. Discussion with relatives confirmed no history of other psychiatric disorders. In the ICU, attempts were made to manage the delirium using benzodiazepines (diazepam, clorazepate), typical and atypical antipsychotics (haloperidol, levomepromazine, risperidone, tiapride), and other drugs (dexmedetomidine, clonidine). The patient was conscious but did not show clear responses to stimuli or contact with the surroundings. He exhibited continuous purposeless movements and occasional gaze fixation. Mechanical restraint was necessary to prevent injury. He only responded to pharmacological sedation.
At the time a psychiatrist was consulted, the patient was receiving tiapride 100 mg/6 hr intravenously, and risperidone 2 mg/12 hr, sertraline 50 mg/24 hr, and diazepam as needed through a nasogastric tube. The psychiatrist recommended discontinuing this medication and starting a continuous infusion of tiapride at a dose of 600 mg in 500 ml of saline solution at a rate of 21 ml/hour, with the possible addition of haloperidol at a dose of 2.5 mg intravenously every 6–8 hours as needed. Propofol was administered at night for sedation.
After 48 hours, during which haloperidol was only administered once every 24 hours, the patient was much calmer, interacted with the surroundings, recognized his relatives, and no longer required mechanical restraint. After 72 hours, he was oriented, calm, and cooperative. He began to take food orally, was able to sit up, and follow simple commands.
Discussion and Conclusion
Delirium is a qualitative disturbance of consciousness that develops as a nonspecific consequence of organic impairment. It is classified into hyperactive, hypoactive, and mixed types. The primary treatment for delirium comprises antipsychotics, most commonly haloperidol. Tiapride is an atypical antipsychotic from the benzamide class. It is a neuroleptic with selectivity for dopamine D2 and D3 receptors. Its biological half-life is only 3–5 hours, which led the doctors in this case to hypothesize that continuous perfusion would ensure a more stable plasma concentration of tiapride. Some studies indicate the safety of this mode of administration and stability in saline solution for up to 48 hours. “Given these findings and the positive development of our patient's condition, we believe that this drug should be considered in the treatment of delirium,” the authors conclude in their case study.
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Source: Calero-Mora C., Cano-Ruiz P., Gómez-Peinado A. Intravenous perfusion of tiapride in a case of treatment-resistant delirium. Actas Esp Psiquiatr 2019; 47 (1): 33–36.
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