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 therapyinduced
organ damage. This is of high relevance in
critically ill patients in whom various norepinephrineinfluenced
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.