Challenges of Delirium Management in Patients with Traumatic Brain Injury: From Pathophysiology to Clinical Practice

Abstract

Traumatic brain injury (TBI) can initiate a very complex disease of the central nervous system (CNS), starting with the primary pathology of the inciting trauma and subsequent inflammatory and CNS tissue response. Delirium has long been regarded as an almost inevitable consequence of moderate to severe TBI, but more recently has been recognized as an organ dysfunction syndrome with potentially mitigating interventions. The diagnosis of delirium is independently associated with prolonged hospitalization, increased mortality and worse cognitive outcome across critically ill populations. Investigation of the unique problems and management challenges of TBI patients is needed to reduce the burden of delirium in this population. In this narrative review, possible etiologic mechanisms behind post-traumatic delirium are discussed, including primary injury to structures mediating arousal and attention and secondary injury due to progressive inflammatory destruction of the brain parenchyma. Other potential etiologic contributors include dysregulation of neurotransmission due to intravenous sedatives, seizures, organ failure, sleep cycle disruption or other delirium risk factors. Delirium screening can be accomplished in TBI patients and the presence of delirium portends worse outcomes. There is evidence that multi-component care bundles including an analgesia-prioritized sedation algorithm, regular spontaneous awakening and breathing trials, protocolized delirium assessment, early mobility and family engagement can reduce the burden of ICU delirium. The aim of this review is to summarize the approach to delirium in TBI patients with an emphasis on pathogenesis and management. Emerging CNS-active drug therapies that show promise in preclinical studies are highlighted.

Keywords: Traumatic brain injury; barbiturates; critical care; delirium; dexmedetomidine; electroencephalography; post-traumatic delirium; xanthohumol..

Fig. (1)

Contributors to delirium in acute TBI. See text (sections 2.1-2.10) for detailed explanations. BBB: Blood-brain barrier; CNS: central nervous system; HPA:hypothalamic/pituitary/adrenal; ICP: intracranial pressure. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (2)

ICU liberation schematic. This schematic depicts symptoms, monitoring tools, and the ABCDEF rounding checklist. From Ely, EW. The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Critical Care Medicine 45(2): 321-330. Used with permission from Wolters Kluwer Health, Inc.

Fig. (3)

Association between performance of the ABCDEF Bundle and risk of symptom-related outcomes the following day from the ICU Liberation study, a multicenter study of 15,226 adults in 68 ICUs. X axes represent proportion of eligible ABCDEF bundle elements performed on a given day, and Y axes represent adjusted probability of a patient experiencing a given symptom-related outcome on the following day. For example, complete bundle performance was associated with an adjusted odds of 0.60 (95%CI 0.49-0.72) of suffering delirium the following day and an adjusted odds of 0.35 (95%CI 0.22-0.56) of suffering coma the following day. From Pun et al., Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Critical Care Medicine 47(1):3-14. Used with permission from Wolters Kluwer Health, Inc.