Protirelin treatment in critically ill severe head-injured patients: A double-blind, placebo-controlled, prospective study

In addition to its neuroendocrine function, thyrotropin releasing hormone (TRH), may act as a neurotransmitter and neuromodulator within the CNS. Data exist to suggest a key role for this drug in the treatment of disturbances of consciousness. In this double-blind, placebo-controlled prospective study, 91 patients with severe head injury (GCS score ≤ 8 for at least six hours) were randomly assigned to receive either placebo or protirelin TRH-T (2 mg 12 hourly) for two weeks. A standard, brain-oriented therapy was otherwise maintained for both groups. The patients were comparable in terms of age, neurological and injury severity scores on admission. Most patients had severe extracranial injuries and/or systemic insults, such as hypoxia and hypotension, in addition to brain trauma. As expected, the mortality rate was high (40.0% protirelin, 58.7% placebo). However, patients treated with protirelin had a shorter duration of impaired consciousness and, therefore, a shorter ICU stay. Furthermore, they showed better functional recovery six months after trauma; 23 of them (51.1%) made a good recovery or had only moderate disabilities, as compared with 13 (28.3%) in the placebo group. Extensive neuropsychological evaluation of this sub-group of patients showed better performance in the protirelin group. However, the small sample size precluded definite conclusions. In conclusion, the present data provide preliminary evidence of the safety of protirelin in the treatment of severe brain trauma.