Phenylephrine vs. Catecholamines and the (rodent) heart

Okay, I don’t normally blog about animal studies, but I thought this would be of interest, particularly to readers of my post ‘Why I don’t give vasopressors in sepsis’ which was followed by some interesting debate between friends Scott, Minh, Aaron and Pete. It supports my view that pure alpha-agonists might fix the numbers on the chart, but are not necessarily helpful in terms of cardiac output and potentially organ perfusion, whereas catecholamines might be more fit for purpose in many shock states including septic shock. If I want to push a ‘pressor’, I use dilute epinephrine, as I think the pure alpha agonists (a group to which norepinephrine does NOT belong) have very few clinical indications – the main one in my view being to counteract iatrogenic vasodilation in the operative anaesthesia setting. I hope this sparks vigorous debate – let’s hear the many ways cats are being skinned out there….

Background: Myocardial depression is a frequent event during septic shock and may mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data are scarce regarding the myocardial effects of vasopressors used to treat hypotension. In this study, the authors compared the effects of three commonly used vasopressors acting on different adrenergic receptors on myocardial function in a rodent model of septic shock, as explored with conductance catheter and positron emission tomography.

Methods: Septic shock was induced in rats by peritonitis. Eighteen hours after septic insult, vasopressors were titrated to increase mean arterial pressure by 20% compared with baseline values.

Results: We observed that peritonitis was associated with arterial hypotension and systolodiastolic dysfunction. Norepinephrine and epinephrine improved mean arterial pressure, cardiac output, and preload recruitable stroke work, a load-independent measure of systolic function, as well as diastolic function and ventriculoarterial coupling. Heart rate, myocardial oxygen consumption, and arrhythmia incidence were furthermore increased in the epinephrine group. Conversely, phenylephrine, a peripheral [alpha]-agonist, exhibited deleterious effects on systolodiastolic function and ventriculoarterial coupling. Conductance catheter and positron emission tomography yielded identical results with regard to myocardial function evolution under vasopressor treatment.

Conclusions: Phenylephrine, a drug without [beta]-1 effects, was associated with decreased ventricular performance and ventriculoarterial uncoupling, whereas epinephrine and norepinephrine improved global hemodynamics and myocardial function in severely hypokinetic and hypotensive experimental septic shock. Nevertheless, epinephrine was associated with increased myocardial oxygen consumption. Thus, norepinephrine appears to be a more reliable and safer strategy as a first-line therapy in this particular setting.

Anesthesiology. 2012 May;116(5):1083-1091

5 thoughts on “Phenylephrine vs. Catecholamines and the (rodent) heart”

  1. I agree with your fundamental philosophy on this, but you can’t get much weaker source than a rat study. Phenylephrine seems fine when you have a situation of pure vasodilation, e.g. a patient you sedate with propofol. If you want inotropy and vasoconstriction, push epi. Push-dose Norepi seems the most clever of all, but someone needs to study this ASAP.

  2. you can’t get much weaker source than a rat study

    I dunno…lizard? earthworm?

    The push-dose norepi style is intriguing, and has been gestating in my mind since you first mentioned it to me.

  3. Vasopressors…. religion…. gossip … clinical medicine…
    Even I think that one should NOT be to judgemental here… after an iatrogenic vasodilatation there is nothing like counteracting it with a pure alfa agonist (if that exsists…)… but if that old one lying on the table, already on some beta-blockers needs a myocardial kick, then why not use an old dirty drug like ephedrine… this all works well in theatre… and in the PHC world… and in the world of medicine…. don’t fix numbers – fix pathophysiology……

  4. great debate. Push dose NORADRENALINE! what a brilliant concept. simple, elegant, totally unstudied as far as I can tell. I give push dose adrenaline all the time so why not noradrenaline? at similar small doses I cannot see any problems. I mean 10-20mcg doses of noradrenaline , even if it gets into sub cut tissue is extremely unlikely to cause harm. Its when you infuse it and it leaks out over an hour or so or if you give higher concentrations that you see issues,

    keeping it all simple makes sense . if you can use one or two agents , like adrenaline or noradrenaline and forget about the rest, to manage your hypotensive patient in a hurry post Induction or for their sepsis or Cardiogenic shock… well in prehospital and retrieval setting..that makes a lot of sense

  5. For temporary hypotension either drug is fine. Only a bridge until meds (eg propofol) fade away or until a central line / IO is placed. Would pick Epi first if I knew of preexisting cardiac depression. Otherwise a coin toss until better data…my 2 cents.

Comments are closed.