Early Autonomic Dysfunction Following TBI and Possible Interventions: A Narrative Review

Traumatic brain injury (TBI) triggers an acute neuroendocrine stress response characterized by a surge of catecholamines (epinephrine, norepinephrine, and dopamine) and activation of the hypothalamic-pituitary-adrenal axis. This early hyperadrenergic "storm," termed early autonomic dysfunction, is initially an adaptive response, but, if prolonged, it can become maladaptive and contribute to secondary brain injury and systemic complications. Elevated circulating catecholamine levels after TBI correlate with worse outcomes and mortality. Dysregulated catecholaminergic signaling has widespread downstream effects following injury: it disrupts normal dopamine/noradrenergic pathways and alters sympathetic/parasympathetic balance, modulates immune responses toward immunosuppression, and impairs vascular and glymphatic homeostasis, leading to cerebral edema. If prolonged, patients can develop chronic paroxysmal sympathetic hyperactivity, which is associated with prolonged hospitalization and poor neurological recovery. Therapeutically, blockade or modulation of adrenergic and related neurotransmitter systems (β-blockers, α2-agonists, GABAergic modulators, dopaminergic drugs, neuromodulation) can mitigate these effects, though controlled data are limited. This narrative review summarizes current understanding of adrenergic dysregulation in TBI and its multisystem sequelae and discusses targeted interventions and future research directions.