Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis.
Am J Respir Crit Care Med. 2016 Jul 11;
Authors: Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M
Abstract
Septic shock is a major cause of death worldwide and a considerable healthcare burden in the 21st century. Recently, attention shifted from damaging effects of the pro-inflammatory response to the detrimental role of anti-inflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to re-evaluate the current management of septic shock and assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude that although novel therapies aimed to reverse immunoparalysis are underway, the use of norepinephrine may aggravate the development, extent, and duration of sepsis-induced immunoparalysis. Current in vitro and animal data indicate that norepinephrine treatment exerts immunosuppressive and bacterial growth-promoting effects, and may increase susceptibility towards infections. However, evidence in humans is circumstantial, as immunologic effects of norepinephrine have not properly been investigated in experimental or clinical studies. Alternatives such as vasopressin/selepressin, angiotensin II, and phenylephrine could have a fundamental advantage over norepinephrine with respect to their immunologic properties. However, also for these agents, in vivo immunologic data in humans are largely lacking. As such, human studies on the immunomodulatory properties of norepinephrine and viable alternatives are highly warranted.
PMID: 27398737 [PubMed - as supplied by publisher]