Controversial Issues Concerning Norepinephrine and Intensive Care Following Severe Traumatic Brain Injury

Abstract

Norepinephrine and corresponding intra- and interorgan pathways are of clinical pathophysiologic and pharmacologic importance as exaggerated activation needs to be reduced and insufficient activation must be supported to prevent further deterioration and therapy-induced organ damage. This is of high relevance in critically ill patients in whom various norepinephrine-influenced organ systems are simultaneousy affected with varying degrees of tolerability and resistance to norepinephrine-induced cell damage and finds its maximal challenge in patients suffering from severe traumatic brain injury (TBI). This comprehensive review describes complex pathophysiologic interactions, including hemodynamic, microcirculatory, hormonal, metabolic, inflammatory, and thrombocytic alterations overshadowed by differential consequences of commonly applied pharmacological interventions following TBI. Overall, investigations published to date suggest that receptor-dependent effects of norepinephrine might predispose to complex evolving deterioration especially during intensive care which is characterized by differentiated complication-driven changes and specific complication-dependent needs. In this context, thrombocytes and leukocytes with their adrenergic receptors and differential norepinephric functional regulation are ideal candidates to influence all organs at once. Despite its secure integration of norepinephrine in clinical routine, future emphasis must be directed at unmasking, monitoring, and controlling possible receptor-mediated detrimental influences which could offset anticipated organ protection.