Phenylephrine vs Norepinephrine in Post Cardiac Surgery Patient

Alex Goodell 8/17/2016

Theory. Phenylephrine (PE) is an alpha-1 agonist with minimal beta-adrenergic affinity.

Norepinephrine (norepi) activates alpha-1, beta-1, and (to a lesser extent) beta-2. Thus PE
produces isolated vasoconstriction, while norepi produces vasoconstriction in addition to a
positive inotropic and chronotropic effect. In the post-cardiac surgery patient, pharmaceutical
management of systemic perfusion is key; this involves balancing vasoconstriction, cardiac
output, venous return, and myocardial demand. It has been argued that norepi may be a
superior medication to phenylephrine for management of post-operative-hypotension
(Stephens 2015), though a recent literature review describes a lack of good head-to-head
evidence and notes that most comparisons are focused on hypotensive patients with preserved
CO (Murfin 2011). Theoretically, the use of a pure vasoconstriction agent without increase
inotropy will increase afterload and may compromise cardiac output. Indeed, PE was associated
with a higher systolic wall stress compared to norepi in 18 post-CAGB patients in a 1993 study
(Goertz). However, in another study, this increased wall stress had no effect on HR or cardiac
index (Butterworth 1990).

Graft flow. There is evidence that phenylephrine reduces flow through bypass grafts. DiNardo
et al (1991) randomized 28 on-pump CABG patients into treatments of epi, norepi, and PE. PE
was associated with a non-significant increase in in saphenous vein graft flow (68 +/- 31 versus
81 +/- 49 ml/min) and a significant decrease in IMA graft flow (40 +/- 16 versus 32 +/- 12
ml/min). Norepi increased saphenous graft flow and showed no change in IMA. Epi increased
both. Another pre/post study, which reported only in an abstract, found that PE infusion
increased flow in radial artery grafts (Skubas 2000).

Splanchnic perfusion. It has been hypothesized that the beta-2 splanchnic dilatation of norepi
may preserve perfusion to the gut. A 2006 cross-over study (Nyguen) of 10 patients found PE
resulted in a statically significant increase in splanchnic vasoconstriction and a greater increase
in splanchnic lactate levels at doses targeting increase of MAP by 30%.

Atrial fibrillation (AF). Because of the ionotropic effect of beta1-stimulation, norepi may
predispose individuals to development of AF compared to those treated with PE alone. Salaria
(2004) studied PE compared to dopamine and dobutamine, finding that beta-adrenergic affinity
was associated with a higher incidence of postoperative AF (dopamine 43% and dobutamine
30% vs phenylephrine 8%, p = 0.05).

Cardioprotection. Mourouzis et al (2014) studies the effects of PE in a rat model. They found
that, compared to untreated controls, PE induced myocardial ischemia.

Conclusion. There is evidence supporting norepi as a safer alternative to PE for maintaining

splanchnic and coronary flow with arterial grafts. Most of evidence for efficacy is from non-
cardiac patients. There are no head-to-head clinical trials comparing the two options with long-
term graft patency or mortality.
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