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.