Phenylephrine impairs host defence mechanisms to infection: a combined laboratory study in mice and translational human study

BackgroundImmunosuppression after surgery is associated with postoperative complications, mediated in part by catecholamines that exert anti-inflammatory effects via the β-adrenergic receptor. Phenylephrine, generally regarded as a selective α-adrenergic agonist, frequently used to treat perioperative hypotension. However, phenylephrine may impair host defence through affinity.MethodsHuman leukocytes were stimulated lipopolysaccharide (LPS) presence or absence of and α- antagonists. C57BL/6J male mice received continuous infusion (30–50 μg kg−1 min−1 i.v.) saline micro-osmotic pumps, before LPS administration (5 mg kg-1 caecal ligation puncture (CLP). Twenty healthy males randomised 5 h (0.5 min−1) receiving (2 ng i.v.).ResultsIn vitro, enhanced LPS-induced production cytokine interleukin (IL)-10 (maximum augmentation 93%) while attenuating release pro-inflammatory mediators. These reversed pre-incubation β-antagonists, but not α-antagonists. Plasma IL-10 levels higher LPS-challenged infused phenylephrine, whereas mediators reduced. Phenylephrine increased bacterial counts CLP peritoneal fluid (+42%, P=0.0069), spleen (+59%, P=0.04), liver (+35%, P=0.09). In volunteers, response (+76%, P=0.0008) plasma concentrations including IL-8 (–15%, P=0.03).ConclusionsPhenylephrine exerts potent effects, possibly involving β-adrenoreceptor. promotes outgrowth surgical peritonitis. therefore compromise patients increase susceptibility towards infection.Clinical trial registrationNCT02675868 (Clinicaltrials.gov).