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Page 4 of 10 Sahulee et al. Vessel Plus 2022;6:5 https://dx.doi.org/10.20517/2574-1209.2021.94

Figure 2. Management strategies for the treatment of low cardiac output syndrome.

Catecholaminergic inotropes
Catecholaminergic inotropes such as epinephrine, dopamine, and dobutamine have long been used in the
cardiac intensive care unit as pharmacologic means to manage LCOS by augmenting cardiac output. They
predominantly activate β-1, β-2, α-1, and dopaminergic receptors. β-1 stimulation increases contractility
through the binding of the actin-myosin complex with troponin C and enhances chronotropy through
calcium channel activation. β-2 stimulation leads to increased calcium uptake by the sarcoplasmic reticulum
leading to vasodilation. Activation of α-1 receptors on arterial vasculature results in smooth muscle
contraction and increases in SVR. The relative affinity of the different catecholamines for the adrenergic
receptors are dose-dependent, vary from drug to drug, and thus are employed to meet specific physiologic
goals. In general, these agents increase contractility and stroke volume and are widely available. However,
the adverse effects of catecholamines are relatively universal in their resultant tachycardia, raised ventricular
end-diastolic pressures, and increased myocardial oxygen demand. Furthermore, the elevation of the SVR,
PVR, or provocation of tachyarrhythmias by these agents can inadvertently cause or exacerbate LCOS. In a
recent survey of cardiac intensivists, epinephrine and dopamine were the most common agents in this class
used to prevent or treat LCOS, and these medications are most commonly started while on or coming off
[14]
CPB . However, in a recent Pediatric Health Information System (PHIS) database review of over 43,000
cardiac surgeries in children, the frequency of use of catecholaminergic inotropes has decreased in the past
[15]
ten years . This is likely due to our better understanding of LCOS and the more recent emphasis on
reducing RV and LV afterload as alternative means to improve oxygen delivery.

Inodilators
Inodilators are medications that have inotropic and lusitropic effects on the myocardium and vasodilatory
effects on the systemic, pulmonary, and coronary vasculature. Milrinone and levosimendan are the most
commonly used medications in this category. Levosimendan, a calcium sensitizer, binds troponin C,
increasing its affinity for calcium and increases inotropy without increasing myocardial oxygen demand. Its
effects are independent of β-adrenergic receptors, and thus its use has a minimal incidence of arrhythmias.
The most commonly reported side effects are headache, hypotension, and hypokalemia. The efficacy and
safety of levosimendan are well reported in adults, but the pediatric literature is sparse and is limited to
observational studies, registry studies, and few randomized control trials (RCT). In a study of 40 infants
[16]
undergoing surgery with CPB managed with either levosimendan or milrinone, Lechner et al.