Delirium and agitation in traumatic brain injury patients: an update on pathological hypotheses and treatment options

Abstract

Traumatic brain injury (TBI) is a global public health epidemic. It represents the principal cause of death and disability in individuals aged under 35 in the USA. In the subacute phase, severe TBI patients who recover consciousness go through a state of agitation and delirium. However, there is only limited research exploring the characteristics of post-traumatic delirium (PTD) although it is likely to be more frequent than in general Intensive Care Unit (ICU) patients. Evidence suggest the incidence of delirium in non-TBI ICU patients is up to 86%. The exact pathophysiological mechanisms underlying the development and progression of delirium in critically ill patients is still unclear. Many hypotheses have been proposed to play a role: neuroinflammation, neurotransmitter imbalance, structural and functional brain damage. TBI patients are at high risk of post-traumatic cognitive impairment, and up to two thirds of patients who survive TBI develop agitation and delirium which is associated with increased disability and long term cognitive impairment. Recommendation for the treatment of PTD in patients admitted to ICU are not clearly identified. Despite the high prevalence of PTD, the condition often goes misrecognized and attributed primarily to the injury itself. There is increasing evidence that certain drugs such as antipsychotics can reduce the incidence and severity of delirium, whereas other drugs such as dexmedetomidine and remifentanil are associated with decreased risk of developing delirium in general ICU patients. However, there is a lack of high quality studies exploring treatment strategies for PTD in the acute setting.