Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension

Abstract

Induction of general anesthesia frequently induces arterial hypotension, which is often treated with a vasopressor, such as phenylephrine. As a pure α-agonist, phenylephrine is conventionally considered to solely induce arterial vasoconstriction and thus increase cardiac afterload but not cardiac preload. In specific circumstances, however, phenylephrine may also contribute to an increase in venous return and thus cardiac output (CO). The aim of this study is to describe the initial time course of the effects of phenylephrine on various hemodynamic variables and to evaluate the ability of advanced hemodynamic monitoring to quantify these changes through different hemodynamic variables. In 24 patients, after induction of anesthesia, during the period before surgical stimulus, phenylephrine 2 µg kg−1 was administered when the MAP dropped below 80% of the awake state baseline value for > 3 min. The mean arterial blood pressure (MAP), heart rate (HR), end-tidal CO2 (EtCO2), central venous pressure (CVP), stroke volume (SV), CO, pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance (SVR) were recorded continuously. The values at the moment before administration of phenylephrine and 5(T5) and 10(T10) min thereafter were compared. After phenylephrine, the mean(SD) MAP, SV, CO, CVP and EtCO2 increased by 34(13) mmHg, 11(9) mL, 1.02(0.74) L min−1, 3(2.6) mmHg and 4.0(1.6) mmHg at T5 respectively, while both dynamic preload variables decreased: PPV dropped from 20% at baseline to 9% at T5 and to 13% at T10 and SVV from 19 to 11 and 14%, respectively. Initially, the increase in MAP was perfectly aligned with the increase in SVR, until 150 s after the initial increase in MAP, when both curves started to dissociate. The dissociation of the evolution of MAP and SVR, together with the changes in PPV, CVP, EtCO2 and CO indicate that in patients with anesthesia-induced hypotension, phenylephrine increases the CO by virtue of an increase in cardiac preload.

Hypotension during hip fracture surgery and postoperative morbidity: a retrospective analysis

“…30 In this context, phenylephrine, metaraminol and noradrenaline infusions are all potential candidates for peripheral short term infusion strategies. 31,32 Ephedrine can also be used by infusion and is effective, though it may lead to more episodes of dysrhythmia. 33 Phenylephrine has been the agent of choice for treating spinal anaesthesia induced hypotension due to its primary vasoconstrictor action, while ephedrine preferentially acts to improve cardiac output.…”

“…34 However, a recent prospective study on the effects of phenylephrine for anaesthesia induced hypotension showed that it was effective at increasing cardiac output in patients who were relatively hypovolemic. 31 Many patients in the hip fracture cohort will have a degree of physiological beta-blockade secondary to age-related autonomic dysfunction, making alpha-1 adrenoceptor agonists the treatment of choice. 34,35 It is not clear whether hypotension is more reliably prevented in high-risk patients by administering intermittent boluses purely when deemed appropriate by the clinician, or by using a continuous infusion.…”

Perioperative Quality Initiative (POQI) consensus statement on fundamental concepts in perioperative fluid management: fluid responsiveness and venous capacitance

“…Alterations in venous tone can change the relative proportions of the unstressed and stressed volumes. For example, alpha adrenergic receptor agonists may increase venous tone and thus increase the stressed volume (and simultaneously lower the unstressed volume), increasing venous return to the heart, raising SV and CO. (Kalmar et al, 2018;Hamzaoui et al, 2010) What is fluid responsiveness? How do we define it, is there variation in proposed definitions, and is there variation from those in clinical practice?…”

Boosting systemic pressure with phenylephrine: arterial or venous modulation?

“…They showed that phenylephrine administration resulted in an increase in cardiac preload, as illustrated by the decrease of both static and dynamic markers of cardiac preload, which increased CO despite the increase in LV afterload, reflected by an increased systemic vascular resistance [1]. The authors suggest the increase in cardiac preload to be the result of an increase in venous return, as they found the pressure gradient driving the venous return to be increased to a greater extent than the resistance to the venous return [6,7].…”

“…In this issue, Kalmar et al elegantly depicted the chronology of the haemodynamic effects, caused by a single administration of phenylephrine, in preload-dependent patients with anaesthesia-induced hypotension. For this purpose, the authors assessed several distinct haemodynamic and nonhaemodynamic indices [6]. They showed that phenylephrine administration resulted in an increase in cardiac preload, as illustrated by the decrease of both static and dynamic markers of cardiac preload, which increased CO despite the increase in LV afterload, reflected by an increased systemic vascular resistance [1].…”